Scientific Presentations
This page lists all the Scientific Presentations by date. If you want to see according to / grouped by product, see left hand navigation.
By Adrián Kalászi, Gábor Imre, Miklós Vargyas, Tímea Polgár (ChemAxon) · March 2010
Four scientists muddy their paws in early phase drug discovery. Bravely our heroes apply ChemAxon’s discovery tools in their challenge. Will they succeed? Will you? All-star toolkit lineup featuring: virtual screening using molecular descriptors, the Screen package, chemical clustering, SAR data analysis, the use of Calculator Plugins, creating and using workflows with KNIME.
Visit postBy Tim Dudgeon (ChemAxon) · March 2010
We provide examples of how a chemistry database can easily be created and deployed to users using Instant JChem. This will illustrate how the database can be built and incorporated into Instant JChem, and how forms can be built for the chemists to use to browse, query and manage the data. New features in Instant JChem that enhance this process will also be described.
Visit postBy Tamás Pelcz (ChemAxon) · March 2010
Review features provided by the JChem for Excel API. How to integrate with existing Excel solutions in VBA, VSTO or COM Add-Ins. Look at how external applications could communicate with JChem for Excel, or read and write JChem for Excel specific workbooks using the Apache POI library.
Visit postIn depth look at how JChem for Excel helps in the drug discovery process. Complete examples covering focused virtual library generation, compound profiling, structure-activity by R-group decomposition, visualization of structural similarity and visualization of descriptors using radar chart.
Visit postThe back-end (chemical engine) products of ChemAxon will be introduced with special focus on latest developments. JChem Base is a chemical database management toolkit to handle molecules, chemical reactions and Markush structures and associated data stored in relational databases. JChem Cartridge provides similar functionality highly integrated into Oracle as well as an SQL interface to other ChemAxon products.
Visit postBy Szabolcs Csepregi (ChemAxon) · March 2010
The ChemAxon Markush project includes drawing, visualization and generation of Markush structures, Markush enumeration techniques and searching. The generic notation includes R-groups, atom and bond lists, link nodes, repeating groups, position variation and homology groups. The project reached a milestone: Markush structures from Thomson Reuters’ MMS(Merged Markush Service) database can now be handled via the Markush DARC file format (.VMN). It will be shown how the contents of this Markush patent database is handled, and recent and near future developments will be introduced.
Visit postBy Attila Szabó, György Pirok (ChemAxon) · March 2010
Chemical structures sometimes contain various drawing errors and those originated from old databases often suffer from the limitations of the early technologies. Having no functions to handle isotopes, stereochemistry, abbreviated groups or metalorganics properly led to “custom representations”, that must be handled during structure registration or the migration of older structures to new chemical databases. The new functionalities of Standardizer provide flexible structural error detection, reporting and reconstruction actions of the encoded structural information. The architecture and some features of the upcoming major Standardizer update are illustrated with examples based on real cases.
Visit postMicrosoft SharePoint Server is becoming the standard portal platform at most major pharmaceutical companies. It lets scientists to easily share and manage research and discovery data. ChemAxon’s SharePoint extensions enable chemistry inside SharePoint not only on the enterprise, but also at the individual level. Manage and filter for structures inside lists, wikis, blogs and discussion boards. Custom calculation field type allows to display structural property predictions in lists. Import from, and export to various chemical file formats.
Most of the information in an organization resides in unstructured data. Use JChem Search for SharePoint to index and find chemical entities within documents on file shares, e-mails, pages from the Internet or corporate intranet.
Visit postBy Tim Dudgeon (ChemAxon) · March 2010
The latest standards for enterprise systems based on the Java platform can provide new approaches bringing type-safety, better support for refactoring, more reuse, extensibility and testability to the development process. However, these approaches have not often been used in the development of chemistry based systems, such as those using Marvin and JChem, which typically still rely on approaches such as JDBC and JSP. We have investigated some of these more promising approaches for building Marvin and JChem based web applications. We will illustrate the use of: – Hibernate and JPA persistence frameworks that make writing database persistence code simpler and less error prone, and show how these can be used with JChem cartridge and JChemBase, – modern component based web frameworks such as Wicket and Grails that promote reuse at the UI layer and allow web based applications or web services to be created with little effort, – alternative languages on the JVM such as Groovy as an to aid productivity and in creating domain specific languages.
Visit postBy Jonathan Lee (ChemAxon) · March 2010
Understand and decide your best interface from the many non-Java programming interfaces to the JChem Suite of tools. Many interfaces will be discussed, such as the pure .Net interface, Oracle Cartridge, Web Services, and workflow platform integrations.
Visit postThe presentation covers the new features and recent improvements of the “ChemAxon for Pipeline Pilot” component collection, as well as our plans for future development.
Visit postBy Tímea Polgár (ChemAxon) · March 2010
Showing one example workflow for a focused library generation; the generated virtual library by Reactor will be further processed to find the most similar compounds to a given active set of compounds.
Visit postLibrary enumeration is a powerful way for the generation libraries containing loads of NON-synthesizable compounds. At least not on that planned synthetic route due to activation/deactivation issues, directing rules and side reactions. The design of virtual reactions will be demonstrated via step-by-step examples: sketching generic reaction scheme, examination of the foreseeable synthetic problems, finding out and formulating solutions to get reusable reactions producing synthetically feasible compounds.
Visit postCan you sketch the structure of Viagra in half minute? Or even in 5 seconds? This presentation shows you tips and tricks that make sketching easier and faster but might have been hidden from you until now. Besides the smart drawing features, built-in hot-keys and abbreviated groups the presentation also shows you how to customize your MarvinSketch to best fit your needs.
Visit postBy Szabolcs Csepregi (ChemAxon) · March 2010
Tautomerism is an important and difficult problem in cheminformatics, and has gained much attention recently. The presentation will focus on ChemAxon’s approaches and algorithms for handling tautomerism.
There are four main topics to cover:
1. The tautomerization calculator plugin is the basis of most methods. It can identify tautomerizable regions, enumerate all or dominant tautomers and predict the distribution of dominant tautomers. Furthermore, it can provide generic and canonical tautomers that are used by the methods discussed. It first identifies possible proton donors and acceptors and finds the tautomerization paths between them. Depending on the desired operation, it then combines the paths into regions (generic tautomer), combinatorially enumerates all possible tautomeric forms (all tautomers), filters and ranks enumerated structures based on pKa and other criteria (dominant tautomers) or canonicalizes using empirical rules (canonical tautomer). The tautomerization plugin is also used to improve results of other calculations, such as macro pKa and logP.
2. Tautomer duplicate search uses generic tautomers combined with a hash key. This method also allows fast filtering of tautomers in chemical database tables. It will be shown how this method is able to handle tautomeric migration of H isotopes and interactions with stereochemistry.
3. Tautomer substructure search enumerates tautomers of the query, and searches each of them separately. In case of query H constraints (explicit H), the constraint is enforced on the tautomeric region to retrieve only true tautomers.
4. Standardizer is a tool for performing custom and built-in transformations on molecules. It is integrated with the JChem chemical database system, so that database and query structures are automatically transformed by the specified transformations. It will be shown how the canonical tautomer and custom transformations can be used to handle tautomerism. Custom transformations also allow handling of ring-chain tautomerism.

The pKa values of 211 discovery (druglike) compounds were determined experimentally using capillary electrophoresis coupled with ultraviolet spectroscopy and a novel fitting algorithm. These values were compared to those predicted by five different commercially available pKa estimation packages:
ACDLabs/pKa, Marvin (ChemAxon), MoKa (Molecular Discovery), Epik (Schrodinger), and Pipeline Pilot (Accelrys). Even though the topological method MoKa was noticeably faster than ACD, the accuracy of those two methods and Marvin was statistically indistinguishable, with a root-mean-squared error of about 1 pKa unit compared to experiment. Pipeline Pilot and EpiK both produced pKa estimates in significantly worse agreement with the experiment. Interestingly, on a number of compounds, the predictions due to ACD v12 were in poorer agreement with the experiment than ACD v10. Microscopic and “apparent” pKa predictions were also compared using ACD v10. Microscopic pKas gave significantly worse agreement with the experiment than the “apparent” values. In all cases, the errors appeared to be randomly distributed across chemical series.
John Manchester*, Grant Walkup, Olga Rivin and Zhiping You
Infection Discovery, AstraZeneca R&D Boston.
J. Chem. Inf. Model., Article ASAP
DOI: 10.1021/ci100019p
Publication Date (Web): March 12, 2010
Original article (at ACS)
Visit postBy Szabolcs Csepregi, Nóra Máté, Róbert Wagner, Szilárd Dóránt, Erika Biró, Tim Dudgeon, Ferenc Csizmadia, Tamás Csizmazia · October 2009
Cheminformatics systems usually focus primarily on handling specific molecules and reactions. However, Markush structures are also indispensable in various areas, like combinatorial library design or chemical patent applications for the description of compound classes.
The presentation will discuss how an existing molecule drawing tool (Marvin) and chemical database engine (JChem Base/Cartridge) are extended to handle generic features (R-group definitions, atom and bond lists, link nodes and larger repeating units, position and homology variation). It will be shown how Markush structures can be drawn and visualized in the Marvin sketcher and viewer, registered in JChem databases and their library space searched without the enumeration of library members. Different enumeration methods allow the analysis of Markush structures and libraries. These methods include full, partial and random enumerations as well as calculation of the library size. Furthermore, unique visualization techniques will be demonstrated on real-life examples that illustrate the relationship between Markush structures and the chemical structures contained in their libraries (involving substructures and enumerated structures).
The presentation will focus on the most recent developments (position variation, repeating units, homology variation), and further developments will be discussed towards full patent handling.
Visit postBy Erika Biró, Ferenc Csizmadia, Nóra Máté, Róbert Wagner, Szabolcs Csepregi, Szilárd Dóránt, Tamás Csizmazia · August 2009
Cheminformatics systems usually focus primarily on handling specific molecules and reactions. However, Markush structures are also indispensable in various areas, like combinatorial library design or chemical patent applications for the description of compound classes.
The presentation will discuss how an existing molecule drawing tool (Marvin) and chemical database engine (JChem Base/Cartridge) are extended to handle generic features (R-group definitions, atom and bond lists, link nodes and larger repeating units, position and homology variation). It will be shown how Markush structures can be drawn and visualized in the Marvin sketcher and viewer, registered in JChem databases and their library space searched without the enumeration of library members. Different enumeration methods allow the analysis of Markush structures and libraries. These methods include full, partial and random enumerations as well as calculation of the library size. Furthermore, unique visualization techniques will be demonstrated on real-life examples that illustrate the relationship between Markush structures and the chemical structures contained in their libraries (involving substructures and enumerated structures).
The presentation will focus on the most recent developments (position variation, repeating units, homology variation), and further developments will be discussed towards full patent handling.
Visit postBy Adrián Kalászi, et al · August 2009
Tackling the conformational flexibility of molecular structures is an innate challenge in most molecular modeling applications ranging from pharmacophore elucidation to virtual screening. Conformational sampling is the most widely used technique to alleviate the computational complexity of modeling flexible three dimensional molecules. Though computationally tractable, yet this approach has some drawbacks.
Most importantly, it is prone to miss biologically relevant conformations. Representing flexible molecules on a continuous scale without the need of discrete sampling provides much higher degree of reliability and accuracy. But how can we address the complexity challenge and cope with the continuous flexibility within a manageable computational time frame?
A flexible 3D alignment method that overlays molecules by optimizing a potential function similar to the intersection of their molecular volumes has been developed. This method, based on the analytical representation of the conformational flexibility, is capable of aligning two or more chemical structures to very high accuracy. Nevertheless, the approach offers reasonable performance for drug-like molecules.
A generalization of the flexible conformational analysis apparatus enables the exploration of the entire conformational space of a molecule. The statistical analysis of this blurred spatial region provides a fairly low dimensional molecular descriptor which serves as the basis for a high throughput 3D virtual screening technique.
Visit postInstant JChem is ChemAxon’s desktop chemistry solution, allowing scientists to manage and search chemical structures and related information. This presentation gives an overview about the most important features of the Instant JChem, it describes the typical users of the tool and gives an idea about the upcoming developments for short and medium terms. The description of the Instant JChem is built around ten bullet points:
- Simple and flexible deployment
- Create and manage structure databases
- Import/export/merge/edit data
- Build tabular and form based reports
- Run combined structure and data searches
- Structure based predictions
- Manage relational data
- Access sophisticated chemistry features
- Collaborate with other users
- Extensible
Among the most typical usage scenarios of the Instant JChem the building of the database is fundamental. Afterwards customers usually use the Instant JChem to create reports from the existing database, share data and customize the tool to fulfill their own needs. The future development of the product contains mostly the synchronization with other JChem releases. It means that the next release of the Instant JChem will improve the database’s server, the schema editor, the handling of the URL fields and probably the Reactor will be integrated to it.
2009 Instant JChem Seminar Series · Feb-March 2009
For the 2009-2010 webinars please click here.
Visit postThe Markush structures describe a compound class by generic notation through R-groups, atom or bond lists, repeating units, position or homology variation, etc. and so they are feasible to define the patent claims and combinatorial libraries. The ChemAxon’s Markush project aims to extend structural search capabilities and enable the Markush enumeration.
The first part of the presentation gives an overview of the existing Markush functionalities, like the features of the combinatorial Markush structure handling, the existing enumeration methods and the Markush structure reduction. The Markush features are implemented as Markush database tables in two chemical databases of the ChemAxon, in the JChem Base and in the Instant JChem. Among the 2009 improvements worth to mention the repeating unit with repetition ranges, the homology groups and the identification of R-group definitions from reagent files.
Regarding the future the ChemAxon’s Markush development plans are related mostly to the patent claims.
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Structural searching techniques are invaluable tools in all cheminformatics systems including but not limited to rational drug design, compound registration systems and laboratory information management systems.
JChem, one of ChemAxon’s major suites of programs, provides a very rich set of features related to structural searches. These features are demonstrated by examples. Covered topics are: substructure, exact, superstructure, MCS (maximum common substructure) and similarity searching. Reaction and R-group searches (including R-logic) are also available, which are complemented by a rich set of query features. SMARTS and query features of the MDL formats are supported.
The database components of JChem are also described: JChem Base and JChem Cartridge for Oracle. An example of a fast MCS-based clustering is also presented.
Finally the recently developed descriptive Chemical Terms Language is demonstrated by powerful structural searches.
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This presentation gives a thorough overview about the component collection that allows you to get access to all ChemAxon tools from Pipeline Pilot. In the introduction part the basic quick facts are provided about the collection.
The major part of the presentation shows the development of the pipeline functionalities within ChemAxon that starts with the description of the available features. Among the most important functionalities the Standardizer, the Reactor, the Marvin applets, the MCS based clustering, the microspecies distribution, the IUPAC name and molecule converter or the burden eigenvalue descriptor are worth to mention. However the presentation puts the focus on the 2008 improvements, on the changes that happened in the versions from 1.2 to 1.4. The features that are emphasized in the presentation are as follows:
- Chemical Terms Calculator
- Canonicalization with Standardizer
- IUPAC naming components
- Changes in Reactor
- Clustering with LibMCS
- JChem Base insert
- JChem Database search
- Improved error reporting
On the closing slides of the presentation the planned components are discussed.
2008 Accelrys European User Group Meeting · 9-12 December 2008.
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The presentation focuses on the differences, similarities, pros and contras of migration from an ISIS environment to a related ChemAxon product. It gives a proper overview about the features of several ChemAxon products, it describes the functionalities of the ISIS tools, you can find independent comparisons, migration case studies and feedback from users and an appendix about the technical resources of ChemAxon products.
The presentation starts with a brief overview of ChemAxon tools like the Marvin family, the Calculator plugins, the Chemical naming, the JChem family, the Markush features, the Standardizer, the drug discovery tools and even the embedded ChemAxon tools.
The first product that is discussed in this presentation is JChem Cartridge. This part starts with the thorough overview of the software’s purpose, features, operators and functions. Afterwards the migration from MDL/Direct cartridge and from ISIS/Host is described through independent comparison and from technical point of view. On the end of this section an overview of a migration questionnaire takes place.
In the next section the ChemAxon’s Standardizer goes through a comparison against the Cheshire including such topics like counting groups, adding explicit hydrogens, group conversion and structure checker.
In the following slides the Instant JChem is compared to the ISIS/Base with special focus on architecture, databases, forms and security. Within the topic of the migration the presentations gives an overview about the comparison of the JChem’s Data Tree and the ISIS Hview and the migration options are explained here thoroughly.
Afterwards comes the brief description of the JChem for Excel and its short comparison to ISIS for Excel. It is followed by the migration of the custom applications including Java applications, .NET applications, web based applications and SOAP.
Finally among the ChemAxon products the migration of the Web Services is discussed.
The presentation closes with the review of the developers’ resources emphasizing the Java API, the Marvin Applets for web applications, the .NET API and native .NET solutions, SOAP interface, AJAX GUI and the integration of ChemAxon components to vendors’ softwares.
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The presentation aims to give an overall understanding of the ChemAxon’s application programming interfaces, graphical user interfaces, additional development informations mostly about Instant JChem and the company’s softwares’ integration.
The main topics of the presentation are as follows:
- Java API
- Marvin Applets for web applications
- .NET API over JNBridge
- Native .NET solution
- JChem Cartridge for Oracle
- SOAP interface
- AJAX GUI
The final slide of the presentation gives an overview about the software vendors that integrated ChemAxon software. For example the Pipeline Pilot, KNIME, Spotfire, Aureus and Integrity are mentioned among the most important vendors.
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The presentation gives a thorough comparison of MDL’s Cheshire and ChemAxon’s tools. Among the alternatives of the Cheshire the presentation lists three ChemAxon functionalities: the Java API, the Chemical Terms and the Standardizer.
In the first few slides the three previously mentioned tools are described. Afterwards the Cheshire, the Java API and the Standardizer is compared to each other from three different point of view:
- Counting Groups
- Adding explicit hydrogens
- Group conversion
In the end of the presentation stands as a summary of the comparison that Java API provides similar flexibility for programmers as Cheshire, though it is a widely used language. The Chemical Terms feature can handle Cheshire codes in the same complexity level but the Chemical Terms expressions can be used in other cheminformatics applications. The Standardizer enables chemists to create conversion rules without encoding.
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By Daniel Bonniot de Ruisselet, Veréb Rita, Miklós Vargyas · August 2008
Chemical names constitute a widely used and convenient way to characterize compounds. Historically, useful compounds have been assigned common names, like toluene. Systematic ways to assign names to all compounds have later been developed and standardized by the International Union of Pure andApplied Chemistry (IUPAC). Such systematic names reveal the presence of characteristic groups, like carboxylic acids and classes of compounds, like esters. Currently, IUPAC is designing precise rules to assign a unique preferred name to each compound, which can be useful, for instance, in the context of patents.
ChemAxon provides tools to generate names from structures, and to generate structures from names. In both cases, we strive to support both traditional and preferred IUPACnames.
236th ACS National Meeting & Exposition · August 17-21, 2008
Visit postBy Szabolcs Csepregi, Nóra Máté, Szilárd Dóránt, Erika Biró, Tim Dudgeon, Ferenc Csizmadia · June 2008
Cheminformatics systems usually focus primarily on handling specific molecules and reactions. However, Markush structures are also indispensable in various areas, like combinatorial library design or chemical patent chemical patent applications for the description of compound classes.
The presentation will discuss how an existing molecule drawing tool (Marvin) and chemical database engine (JChem Base/Cartridge) are extended to handle generic features (R-group definitions, atom and bond lists, link nodes and position variation). It will be shown how Markush structures can be drawn and visualized in the Marvin sketcher and viewer, registered in JChem databases and their library space searched without the enumeration of library members. Different enumeration methods allow the analysis of Markush structures and libraries. These methods include full, partial and random enumerations as well as calculation of the library size. Furthermore, unique visualization techniques will be demonstrated on real-life examples that illustrate the relationship between Markush structures and the chemical structures contained in their libraries (involving substructures and enumerated structures).
The presentation will focus on the most recent developments, and further developments will be discussed towards full patent handling.
8th International Conference on Chemical Structures (ICCS) · June 1-5, 2008
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By Miklós Vargyas, Judit Papp, Ferenc Csizmadia, Szabolcs Csepregi, Ákos Papp, Péter Vadász · June 2008
Clustering chemical structures is a widely used method in various phases of the drug discovery process. Possible applications range from clustering virtual hit sets consisting of 1000’s of structures to clustering million member compound libraries.
Traditional clustering methods are based on similarity scores. These techniques are highly efficient from a bare computational point of view but results are often hard to interpret, even by experts.
A clustering technique that results in highly intuitive grouping of structures can be introduced by the use of the concept of maximum common substructure (MCS).
8th International Conference on Chemical Structures (ICCS) · June 1-5, 2008
Visit postBy György Pirok, Zsolt Mohácsi, Nóra Máté, József Szegezdi, István Cseh, Attila Szabó, Miklós Vargyas, Szabolcs Csepregi, Ákos Papp, Ferenc Csizmadia · June 2008
Pharmaceutical research is not just about molecules, it is about realizable molecules having certain properties. The available set of computable properties is growing, each function usually calculates a specific physicochemical parameter. These functions, like partial charge distribution, p , logD carry important chemical information, but the most interesting questions today are more complex.
Many questions are related to ADMET. Will a planned specific compound be absorbed well, what are its major metabolites, how will it behave in a certain reaction, will it be biologically active?
Scientists need an easy way to formulate calculations by the combination of property predictions,mathematical functions, and substructure matching functions. The Chemical Terms language was developed with this purpose in mind. More than a hundred functions are currently provided, and can be extended through a public plugin interface. The evaluator engine is an integratable component, which provides instant evaluation of Chemical Terms expressions entered as text. The Chemical Terms language has been used to improve the chemical feasibility of various cheminformatics tools such as database filtering, pharmacophore screening, drug design, virtual synthesis and metabolic pathway prediction.
8th International Conference on Chemical Structures (ICCS) · June 1-5, 2008
Visit postPipeline Pilot solutions are based around a powerful client-server platform that lets you construct workflows by graphically combining components for data retrieval, filtering, analysis, and reporting. ChemAxon implemented these functionalities to a number of its products that are described in this presentation as for 2008.
After the introduction of the ChemAxon’s product line the presentation starts to give an overview about the products that implemented Pipeline Pilot: Marvin Sketch, Marvin View, the Calculator Plug-ins or Chemical Terms. Among the ChemAxon tools the JChem Base is emphasized as several features and interfaces were added to that. Most of the innovations improved the searching facility of the database manager through concentrated functionality. The next important development the presentation talks about is the canonicalization functionality of the Standardizer that is simple to use but it can handle complex tasks too. The virtual synthesis of the ChemAxon’s Reactor was updated with Pipeline Pilot solutions as well to make the tool more effective, flexible, smart and compatible. The Pipeline Pilot was implemented to the Instant JChem as well to create and update databases that can be intuitively searched and analyzed. On the last few slides there’s an overview about the plan of the current and future developments, the list of the available components and the ones that are planned to become a component.
2008 SciTegic Pipeline Pilot User Group Meeting, March 5-7, 2008
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By József Szegezdi, Ferenc Csizmadia · August 2007
The ChemAxon added a new Calculator Plugin to the Marvin and JChem product families in 2007 to generate the tautomeric structures of a molecule. The new functionalities offer a wide range of solutions for users from simple tautomer generation to the prediction of tautomer distribution for different pH values.
In the first paragraph of the presentation the method of the tautomer calculation is described thoroughly. Afterwards the concept of the dominant tautomers are explained that enables to generate all tautomers of the submitted molecule even the very unstable examples that have no practical significance. This is followed by the description of the canonical tautomers that are relevant in duplication filtering during compound registration. For the deeper understanding of the ChemAxon’s tautomer generation methods the calculation of the tautomer distribution is described through several examples and even two concrete test cases are provided in the end of the presentation.
American Chemical Society Fall meeting, Aug 19-23rd, 2007
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By Daniel Bonniot de Ruisselet, Ferenc Csizmadia · March 2007
The standardization of the chemical nomenclature is an old-established issue within the chemists’ community. The IUPAC standardization was created first in 1921. This presentation gives an overview about the challenges of the IUPAC naming in cheminformatics softwares and talks about the ChemAxon’s solutions for this problem.
The major problems with the IUPAC naming is discussed in the first part of the presentation. Among these issues you can read about the difficulties of using the rules to define the principal chain of a structure, the method of the dearomatization and the problems to name the bridged cyclic structures. A solution for this issue was implemented in ChemAxon’s Marvin family. In the evaluation part of the presentation you can find an overall comparison of the Marvin and its competing products including even the manual naming. Besides the Marvin family the IUPAC naming functionality can be used in other tools as well. For example it is implemented in the Marvin Sketch as an interactive, real-time naming function; the Instant JChem contains a batch naming feature etc.
American Chemical Society Spring meeting, March 25-29th, 2007
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By József Szegezdi, Ferenc Csizmadia · March 2007
A method was developed for predicting of the aqueous ionization constants (pKa) of organic molecules. The method is a based on empirically calculated physico-chemical parameters that are obtained from ionization site-specific regression equations.
The presentation starts with the description of the ChemAxon’s pKa calculation method. It is built around the pKa of the monoprotic molecules that is calculated as the sum of the next three increments. The explanation includes that the pKa calculation of multiprotic molecules is governed by a theoretically derived kinetic equations in our model and it describes the effect of tautomerization and resonance that can be taken into account in pKa prediction. You can read about the acidic and basic groups that are available in the ChemAxon’s pKa model. Afterwards the presentation goes for the title topic and defines the small and large models of pKa calculations that is followed by a testing of these models. The implementation of the ChemAxon’s pKa calculator to the company’s Marvin and JChem software suits is described in the last part of the presentation.
American Chemical Society Spring meeting, March 25-29th, 2007
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By György Pirok, Attila Szabó, Ferenc Csizmadia, István Cseh, József Szegezdi, Miklós Vargyas, Nóra Máté, Szabolcs Csepregi, Zsolt Mohácsi · March 2007
This presentation gives an overall understanding about ChemAxon’s Chemical Terms which is a simple but extensible language, a general interface to combine chemical functions for various cheminformatics purposes. Briefly the Chemical Terms enables the software programs to extend their “chemical intelligence”.
On the first slides of the presentation you can read about the problems that belong to the topic of the Chemical Terms. The related questions are listed within four categories: virtual reactions, filtering, pharmacophore mapping and random evolutionary de Novo drug design. The following slides give the answers for these questions presenting the development of the Chemical Terms functionality to solve the above mentioned chemical problems. Afterwards you can read about the Chemical Terms’ function examples including substructure matching, chemical calculations, the calculation of returning molecules and combining functions in the tools. In the end of this part of the presentation the Chemical Terms Editor is introduced in a few words.
The major part of the presentation focuses on the ChemAxon applications that the Chemical Terms functionality is built in. The Instant JChem, the filters of the Pipeline Pilot, the Reactor, the Metabolizer are mentioned in this section. Finally an overview of the upcoming Chemical Terms features is discussed in three major groups: simplified syntax, simplified editing and new functionalities.
American Chemical Society Spring meeting, March 25-29th, 2007
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By Miklós Vargyas, Judit Papp, Ferenc Csizmadia, Szabolcs Csepregi, Alex Allardyce, Péter Vadász · September 2006
Clustering chemical structures is a widely used method in various phases of the drug discovery process. Possible applications range from clustering virtual hit sets consisting of 1000’s of structures to clustering million member compound libraries.
Traditional clustering methods are based on similarity scores. These techniques are highly efficient from a bare computational point of view but results are often hard to interpret, even by experts.
A clustering technique that results in highly intuitive grouping of structures can be introduced by the use of the concept of maximum common substructure (MCS).
American Chemical Society National Meeting. 11-14 September, 2006.
Visit postBy Gábor Imre, Adrián Kalászi, Imre Jákli, Ödön Farkas · August 2006
Numerous theoretical methods in the field of computational chemistry fall back on the availability of 3D structures of compounds. Determining molecular structure without human interaction is an essential component of several techniques, like QSAR, 3D pharmacophore analysis, reaction prediction, etc.
Moreover, current computational tools used for structure determination, including force-fields and quantum chemical methods, require a complete set of initial 3D coordinates. The efficiency of 3D structure based HTS (high throughput screening) tools also can be enhanced by employing conformational analysis to yield multiple valid structures.
Our approach utilizes a composition of several methods ranging from pure rule based1, multi dimensional distance geometry method2 to stored substructure lookup features in a flexible software framework. The actual implementation is a highly portable JAVA software, which fits in a broad scale of applications: it can be used in small web drawing applets3 as well as a standalone database processing component.
The coordinate determination process is characteristically a “divide and conquer” approach: the structure is composed of fragments, which are joined together. From the available fragment conformers, the conformers of the joined structures can be generated during the fuse step. The fragment conformers are generated either through further fragmentation or with an elemental structure/conformer prediction method, consequently the conformational analysis is an inherent part of the building process (in contrast with methods proceeding from 3D initial structures4). The novelty of our approach lies in the diversity of the utilized elemental
methods and the arisen scalability options.
1st European Chemistry Congress, Budapest, Hungary, 27-31 August, 2006.
Visit postBy György Pirok, Alex Allardyce, Ferenc Csizmadia, István Cseh, Nóra Máté, Péter Kovács, Szabó Attila, Szabolcs Csepregi, Szilárd Dóránt · August 2006
The Standardizer is a customizable chemical structure conversion tool that was developed by the ChemAxon. This presentation gives a thorough overview about this tool. The introduction of the Standardizer starts with the explanation of the goals of the tool that are discussed in three large topics: canonicalization, beautification and modification.
The first part of the presentation focuses on the canonicalization: it describes the solutions of the Standardizer through examples of handling the tautomers, hydrogens, resonant structures, mesomers, fragments and removing the solvents and the specific counterions. The next slides of the presentation describe the fundamental problems that are related to the beautification with a special focus on the cleaning methods of the Standardizer. This section includes a description of the database usage of the tool.
After the short overview of the modification the presentation focuses on the appearance and applications of the Standardizer: it introduces the tool’s GUI, the Virtual Synthesis and the structure databases as applications.
Workshop Chemoinformatics in Europe: Research and Teaching, May 29-June 01, 2006
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By György Pirok, Nóra Máté, István Cseh, Attila Szabó, Szilárd Dóránt, Zsolt Mohácsi, Péter Kovács, Szabolcs Csepregi, Alex Allardyce, Ferenc Csizmadia · July 2006
A chemical compound can appear in various forms and its graphical representation often depends on the taste of the chemist. These variants are usually represented with different graphs in chemical software programs making the structural identification difficult.
Apart from the naturally occurring mesomeric and tautomeric issues, chemical compounds are rarely neutral and pure, thus counterions and solvents might appear in the chemical structure files making the identification even more problematic.
ChemAxon1 developed Standardizer, a Java-based software tool for the batch conversion of chemical structures according to a standard defined by the chemical database administrator.
Visit postBy György Pirok, Alex Allardyce, Ferenc Csizmadia, István Cseh, Nóra Máté, Péter Kovács, Szabó Attila, Szabolcs Csepregi, Szilárd Dóránt · June 2006
The Standardizer is a customizable chemical structure conversion tool that was developed by the ChemAxon. This presentation gives a thorough overview about this tool. The introduction of the Standardizer starts with the explanation of the goals of the tool that are discussed in three large topics: canonicalization, beautification and modification.
The first part of the presentation focuses on the canonicalization: it describes the solutions of the Standardizer through examples of handling the tautomers, hydrogens, resonant structures, mesomers, fragments and removing the solvents and the specific counterions. The next slides of the presentation describe the fundamental problems that are related to the beautification with a special focus on the cleaning methods of the Standardizer. This section includes a description of the database usage of the tool.
After the short overview of the modification the presentation focuses on the appearance and applications of the Standardizer: it introduces the tool’s GUI, the Virtual Synthesis and the structure databases as applications.
Workshop Chemoinformatics in Europe: Research and Teaching, May 29-June 01, 2006
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By Miklós Vargyas, Judit Papp, Alex Allardyce, Ferenc Csizmadia · March 2006
An ever increasing number of molecular structure visualization tools are being developed by cheminformatics companies, academic research labs and recently by the open source community. Many of these tools have become popular and are widely used by professional researchers, public websites providing chemistry data and also for educational purposes.
It also has to be admitted, that these software work well, they provide good image quality, are rich in features and do not show stability or performance problems. So why implement “yet another molecular structure visualization software”?
ChemAxon already has an active chemical editor and viewer development as well as a plugin technology for property prediction. From our users and own experience we felt that none of the existing visualization tools provided all of the key features in one device and that some functionalities are not available, particularly;
- web-enabled high quality rendering
- managing very large complexes
- all types of common molecular surfaces are available
- molecular properties are mapped on surfaces
- interactive monitors and controls
- platform independent
- available as programmers toolkit (Java API)
- professional support
MarvinSpace, ChemAxon’s new 3D molecule visualization and modeling software aims to achieve a wide spectrum of functions combined with near print quality interactive rendering in a platform independent solution. MarvinSpace should be useful for content providers, online publishers, public internet databases, chemoinformatians, medicinal chemists, modelers and biochemists.
InfoTechPharma, 13 – 16 March 2006
Visit postBy Péter Kovács, Szilárd Dóránt, Szabolcs Csepregi, Nóra Máté, György Pirok, Ferenc Csizmadia · March 2006
JChem Cartridge adds chemical knowledge to the Oracle platform. Data can be searched by structure, substructure and similarity criteria through extending Oracle’s native SQL language. Chemical data can be easily inserted and modified using SQL.
JChem Cartridge relies on Oracle’s extensible indexing framework for best search performance. In order to take advantage of this capability, the index type has to be applied.
InfoTechPharma, 13 – 16 March 2006
Visit postBy György Pirok, Nóra Máté, Jenő Varga, József Szegezdi, Miklós Vargyas, Szilárd Dóránt, Ferenc Csizmadia · January 2006
Predicting “realistic” compounds of given chemical reactions with virtual synthesis tools usually requires the manual intervention of experienced chemists in the enumeration phase for the selection of appropriate reactants, assignment of the corresponding reaction sites, and removal of the unlikely products.
To automate the virtual synthesis process, we have moved the expertise intensive parts from the compound library design phase to the reaction library design phase. ChemAxon is building an in silico reaction library containing important preparative transformations, where each reaction definition contains a generic transformation scheme and additional rules to handle the various starting compounds according to the corresponding chemo-, regio-, and stereoselectivity issues. Having well designed reaction definitions in hand, our software tool is able to generate synthetically feasible compound libraries with minimal effort in the enumeration phase.
By Miklós Vargyas, Judit Papp, Alex Allardyce, Ferenc Csizmadia · August 2005
An ever increasing number of molecular structure visualizaton tools are being developed by cheminformatics companies, academic research labs and recently by the open source community. Many of these tools have become popular and are widely used by professional researchers, public websites providing chemistry data and also for educational purposes.
It also has to be admitted, that these softwares work well, they provide good image quality, are rich in features and do not show stability or performance problems. So why implement “yet another molecular structure visualization” software?
- Well, ChemAxon already has active chemical editor and viewer development as well as a plugin technology for property prediction. From our users and own experience we felt that none of the existing visualization tools provided all of the key features in one device and that some functionalities are not available, particularly;
- web-enabled high quality rendering
- very large complexes are managed
- all types of common molecular surfaces are
- available
- interactive monitors and controls
- platform independent
- available as programmers toolkit (Java API) plus: professional support
public development directly driven by users’ needs MarvinSpace, ChemAxon’s new 3D molecule visualization and modeling software aims to achieve a wide spectrum of functions combined with near print quality interactive rendering in a platform independent solution. MarvinSpace should be useful for content providers, online publishers, public internet databases, chemoinformatians, medicinal chemists, modelers and biochemists.
Drug Discovery Technology & Development, August 9-11th, 2005
Visit postNumerous theoretical method in the field of computational chemistry falls back on the availability of 3D structural information about compounds. Determining molecular structure without human interaction is an essential component of several techniques, like QSAR, 3D pharmacophore analysis, reaction prediction, etc. Current computational tools used for structure determination including force-fields and quantum chemical methods, even require a complete set of initial 3D coordinates. The efficiency of 3D structure based HTS tools also can be enhanced by employing conformational analysis to yield multiple valid structures.
Our approach utilize a composition of several methods ranging from pure rule based multi dimensional distance geometry method to data based stored substructure lookup features in a flexible software framework. The actual implementation is a highly portable JAVA software, which fits a broad scale of applications: it is used in small web drawing applets as well as standalone database processing component.
The coordinate determination process can be best characterized by the “divide and conquer” approach: the structure is composed of fragments, which are joined together. From the available fragment conformers the conformers of the joined structures can be generated during the fusing step. The fragment conformers are generated either through further fragmentation or with an elemental structure/conformer prediction method, consequently the conformational analysis is an inherent part of the building process. The novelty of our approach lies in the diversity of utilized such elemental methods and the arisen scalability options.
7th International Conference on Chemical Structures, 5-9 June 2005
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By Szabolcs Csepregi, Szilárd Dóránt, Nóra Máté, Miklós Vargyas, Péter Kovács, György Pirok, Ferenc Csizmadia (ChemAxon) · March 2005
Molecular search techniques are invaluable tools in all cheminformatics systems including rational drug design, compound registration systems and laboratory information management systems. Often they provide a basis for more complex applications like functional group identification, bond cleavage, virtual reaction processing, standardization, toxic fragment identification, etc.
JChem, one of ChemAxon’s major suites of programs, provides a very rich set of features related to structural search which is described in this presentation from different points of view: interfaces and options, database solutions, formats and platforms, the performance of the JChem Base. The Oracle was extended to support chemical database operations through JChem Cartridge for Oracle which has got two examples in this presentation: SQL examples and SQL examples using Chemical Terms. The JChem tools can handle a wide variety of query features that are detailed below:
- Atom query features
- Query of SMARTS atoms
- Bond and fragment query features
- E/Z double bond stereo searching
- Tetrahedral Chirality
- Reaction search
- R-group search
- Explicit and implicit hydrogens
- Canonicalization
ChemAxon’s JChem suite contains a broad range of chemical search facilities with a rich set of features besides the above mentioned ones. The final part of the presentation gives a proper overview about the Chemical Terms language, the Similarity search, the Maximum Common Subgraph and R-group decomposition. All the tools mentioned in this presentation are 2005 releases and built 100% on Java platform.
9th Annual InfoTechPharma® Conference, 15-16 March, 2005.
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By György Pirok, Nóra Máté, Jenő Varga, Miklós Vargyas, Szilárd Dóránt, Ferenc Csizmadia · March 2005
The computational description of chemical structures is a well established area. The field of synthetic chemistry, however, still does not have adequate software tools, since preparative chemistry is an experimental science full of unexpected transformations.
The mathematical foundation is too complicated to solve and there is no standard method to describe the valuable knowledge of experienced synthetic chemists in exact formulas, which could be evaluated by computers. In the scope of this presentation, we will introduce ChemAxon’s approach for modeling reactions, a software component able to generate synthetically feasible products and some interesting applications of this technology.
The number of known compounds is permanently growing, currently, more than 24 millions are registered in the Chemical Abstracts
1. But this is only a teeny-weeny part of the realizable molecules. The estimated number of realizable molecules is so high due to the wonderful variability of organic elements
2. Even much higher than the number of atoms in the Universe, which can be estimated from its mass
3. Our current technology does not enable us to synthesize and test most of the possible compounds in the foreseeable future, thus, we need something much faster and cheaper than preparative or combinatorial synthesis helping us to select those few molecules worth to be synthesized.
9th Annual InfoTechPharma® Conference, 15-16 March, 2005.
Visit postBy Szabolcs Csepregi, Szilárd Dóránt, Nóra Máté, Miklós Vargyas, Péter Kovács, György Pirok, Ferenc Csizmadia · November 2004
The molecular search techniques represent an extremely wide range of solutions in all cheminformatics systems. This presentation starts with highlighting some crucial examples of applications: compound registration, database search, pharmacophoric group identification, functional group identification, cleavage bond identification, virtual reaction procession, standardization, toxical fragment identification.
JChem, one of ChemAxon’s major suites of programs, provides a very rich set of features divided into two major groups: one is atom by atom search (ABAS) or structural search, the other is similarity search. The following slides describe the structural search in the ChemAxon’s JChem Base. The Oracle was extended to support chemical database operations through JChem Cartridge for Oracle which has got examples about using substructure and similarity searches and Chemical Terms examples. The JChem tools can handle a wide variety of query features that are detailed below:
- Atomic features
- Atomic SMARTS features
- Bond and components features
- Double bond stereo search
- Tetrahedral chirality stereo search
- Reaction search
- R-group search
- Hydrogens
Afterwards you can read about the functionalities that are related to the structural search: Standardizer, similarity search, R-group decomposition and pairs of molecules. Among these tools the Chemical Terms is emphasized in this presentation. The new Chemical Terms language is a beneficial complement to structural searches allowing data mining made easy.
Applications of Cheminformatics and Chemical Modelling to Drug Discovery, 8-19 November 2004
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By Szabolcs Csepregi, Ferenc Csizmadia, Szilárd Dóránt, Nóra Máté, György Pirok, Zsuzsanna Szabó, Jenő Varga, Miklós Vargyas · July 2004
From virtual screening to de novo drug design, there is a wide spectrum of tools available for computer aided drug discovery. The methods developed have their strengths as well as their weaknesses.
On one end of the spectrum virtual screening techniques, for instance, are fast and guarantee the availability of virtual hits for in vitro tests. However, the set of available chemicals is limited (10 000 000 is probably a good upper estimation for the number of known chemicals) and this implies a limited usability of virtual screening.
Towards the other end of the spectrum of discovery tools de novo drug design methods try to alleviate the problem of a finite compound space by suggesting novel molecular structures. Often, these are assembled by linking small molecular fragments in a procedure which is more or less chemically unaware. As a consequence the synthetic accesibility of de novo designed ligands is often a problem.
A method, which combines advantages of virtual screening with advantages of de novo design while eliminating their disadvantages has been implemented. This method deploys virtual screening over an ever growing space of virtual compounds that are likely to be synthetically accessible. To achieve this, commercially available chemical structures are combined by smart chemical reactions . These, unlike generic reaction equations that generate all possible products that are topologically relevant, are capable of eliminating products that are unlikely to be accessible via chemical synthesis.
In addition to synthetic accessibility there is another advantage of this method: no design is involved during structure generation. Consequently structures will be diverse both chemically and biologically and they can be screened for various targets simultaneously or at a later time so no potential lead is lost.
The applicability and efficiency of the method will be demonstrated with various examples.
Workshop on Chemical Information, July 2, Lausanne, Switzerland
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By József Szegezdi, Ferenc Csizmadia · April 2004
A new method for predicting the aqueous ionization constants (pKa) of organic molecules has been developed in 2004. The method is based mainly on empirically calculated partial charges. Hydrogen bonds are also parameterized and taken into account within the calculation.
The presentation explains how ChemAxon approaches the problem of pKa calculation. First the method of the pKa calculation is explained and it is followed by an example of a pKa partial charge distribution. The second part of the presentation focuses on the modeling of intramolecular hydrogen bond (IHB). After a preliminary data preparation, altogether 1670 molecules were used for testing the performance of the pKa calculation model.
All the pKa calculations are available in ChemAxon’s Marvin and JChem suites.
227th ACS National Meeting, Anaheim, California · March 28 – April 1, 2004
Visit postBy József Szegezdi, Ferenc Csizmadia · April 2004
A new method has been developed for predicting the octanolwater distribution coefficient of organic molecules. The prediction of log based on empirically calculated micro ionization constants, p , and micro partition coefficients, logp.
The micro ionization constant is obtained from empirically calculated partial charge distribution of a molecule. The calculation of micro partition coefficient, logD , is based on atomic fragment values. Micro partition coefficient of ionized microspecies, also calculated from atomic fragment values. The ionic strength and zwitterionic effect on log is also included in the log calculation.
227th ACS National Meeting, Anaheim, California · March 28 – April 1, 2004
Visit postBy Miklós Vargyas, Zsuzsanna Szabó, Ferenc Csizmadia, György Pirok, Modest von Korff, Mathias Steger · April 2004
Choosing the right combination of the available descriptors is a tedious work when a virtual screening experiment is set up. Additionally, some descriptors may allow several parameters that increase the degrees of freedom dramatically. Finally, when comparing descriptor values one can choose from numerous dissimilarity metrics. To cope with this freedom of choice an automated optimization tool has been implemented.
This tool, which can be considered as an alternative to dimension reduction applied in QSAR, has proved to be successful in helping chemists to choose suitable descriptors, metrics and parameter values for virtual screening. It will be demonstrated that optimization can increase the hit ratio of the virtual screening procedure by 1 to 3 orders of magnitude.
227th ACS National Meeting · March 28 – April 1, 2004 · Anaheim, California
Visit postBy György Pirok, Nóra Máté, Szilárd Dóránt, Miklós Vargyas, Ferenc Csizmadia (ChemAxon) · April 2004
High throughput screening initiated a new gold-rush in drug discovery. Although the reef of combinatorial chemistry has enriched the pharmaceutical industry with many new biologically active compounds, there is a growing demand to access new molecules even before they are synthesized.
Huge virtual libraries can be generated by computer programs, but the quality of the results depends on technology of reaction modeling. It is a hard nut to crack, since preparative chemistry is not an abstract science and theory often fails in practice.
The ideal virtual reaction library contains a few hundred generic reactions equipping chemists with classified preparative transformations. Furthermore, the ideal virtual reactions are specific to generate chemically feasible products from each individual compound. So, how can a generic reaction be specific?
227th ACS National Meeting · March 28 – April 1, 2004 · Anaheim, California
Visit postBy Szabolcs Csepregi, György Pirok, Miklós Vargyas, Nóra Máté, Mathias Steger, Modest von Korff, Ferenc Csizmadia · March 2004
JChem AnalogMaker is a program for de novo design and lead optimization. It uses an evolutionary search algorithm to optimize fragment-built molecules against a user customizable goal function.
The goal function is formulated by the user in our Chemical Terms language, which includes the description of (dis)similarity (e.g. pharmacophore similarity to a set of known actives, chemical dissimilarity from licensed drug molecules), property calculations (pKa, logD, logP, polar surface area, partial charge, etc.), substructure searches and Lipinski-like rules.
To target synthetic accessibility, the building blocks of the generated candidate molecules are fragments resulting from our Fragmenter tool. The Fragmenter tool cleaves molecules of a library based on RECAP cleavage rules or the user’s own reaction equations. In this way all fragment connections made by AnalogMaker correspond to transformations having synthetic equivalents.
The evolutionary optimization algorithm is also highly customizable and incorporates elements from genetic algorithms, simulated annealing and TOPAS.
227th ACS National Meeting · March 28 – April 1, 2004 · Anaheim, California
Visit postBy Miklós Vargyas, Zsuzsanna Szabó, György Pirok, Ferenc Csizmadia, Modest von Korff, Mathias Steger · November 2003
Drug research is often termed as searching for a needle in a haystack. Virtual screening is widely recognised as a valuable tool to effectively reduce the size of the ‘haystack’ by about one order of magnitude. In this presentation a technique that can further improve the efficiency of the screening procedure is proposed.
We focus on topological pharmacophore similarity based search where only a set of known active 2D structures is known. The pharmacophores of these structures are analysed by perceiving the pharmacophoric characteristic of each individual atom. Pharmacophore patterns are transformed into a topological cross correlation histogram. These correlation histograms are molecular descriptors that represent the pharmacophoric character of structures in a mathematically tractable form. Proximities (metrics) like the Euclidean distance and the Tanimoto coefficient are applied to estimate the dissimilarity between two such descriptors. The canonic formulae of the proximities are extended with weights and other parameters to help bias the metrics behaviour when comparing two compounds. Parameters are optimized in an automated training process that uses a subset of the target library and a subset of the known active structures. The optimized proximities are then passed on to an independent validation stage, which evaluates by calculating the enrichment ratio achieved within the virtual screening process.
Optimized virtual screening is capable of reducing the size of the ‘haystack’ by another order of magnitude (in some cases an even higher reduction is achieved) and it can also lead to scaffold hopping. The method is generic enough to adapt to other molecular descriptors and metrics. The efficiency of the method and cross-validated results will be presented.
eCheminformatics 2003, November 10-15, 2003
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By György Pirok, Nóra Máté, Szilárd Dóránt, Miklós Vargyas, Szabolcs Csepregi, Ferenc Csizmadia · November 2003
Modeling chemical structures is a scientifically well grounded area, proving it’s self in theory as well as in practice. However, there are many traps on the road to virtual reaction processing.
Chemical Terms turn generic reaction equations to “smart” transformations. Smart transformations are generic, since they can be applied to whole compound libraries. Smart transformations are specific as well by „knowing” reactivity and selectivity rules they handle each compound specifically. Awell defined library of smart transformations can form the basis of various applications, such as virtual synthesis, retrosynthesis, fragmentation, structure canonization and metabolism analysis. Chemical Terms as a general chemical expression format, enables chemists to define complex conditional expressions in a standard format like structure queries and advanced pharmacophore point definitions.
eCheminformatics 2003, November 10-15, 2003
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By Gábor Imre, Gábor Veress, András Volford, Ödön Farkas · September 2003
In the field of computational chemistry it is usual to have only a partial set of structural information about compounds, like the connectivity or the formula. Individual studies can easily be performed using ‘human interfaces’ for building input structures.
However, automatic, ‘batch’ processes cannot be applied on a large number of molecules if they imply human intervention. Studies, like QSAR, pharamacophore analysis, reaction prediction might need full, complete 3D information for the compounds of interest. The widespread tools used for structure determination (force-fields or quantum chemical methods) even require a complete set of initial 3D coordinates.
Our approach intends on generating globally valid set of 3D coordinates for small and medium sized molecules, based on local structural criteria. Over against iterative, backtrack based structure predicting algorithms, our method is capable of satisfying partially inconsistent requirements. Such situations are common for structures holding polycyclic, rigid details.
Goals mentioned above can be achieved using coordinates interpreted in a space with a Minkowski metric. Our coordinate assignment process is divided into the following parts: (I) Automatic generation of distance criteria based on chemically relevant local properties, such as bond stretches, bond angles, dihedral angles, etc. (II) Multi-dimensional coordinate assignment which fulfills all the criteria. (III) Geometry optimization using a force field extended to the multi-dimensional Minkowski space. The optimization eliminates the over-3D components and yields the 3D coordinates.
Journal of Molecular Structure (Theochem), 666-667 (2003) 51-59
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By Miklós Vargyas, Zsuzsanna Szabó, Korff Modest, György Pirok, Ferenc Csizmadia, Mathias Steger · September 2003
The efficiency of virtual screening in drug discovery greatly depends on three factors: (1) pharmacophore point perception (2) representation of molecular structures with a descriptor, (3) dissimilarity metric to capture matching patterns in the descriptors. In this presentation methods tackling all three key factors will be discussed.
Pharmacophore point perception relying on the calculation of the protonation state of atoms and the partial charges at a user-defined pH assigns generalized types to atoms. Topological cross-correlation of these generalized atom types provides a compact representation of pharmacophores, however, the flexibility and shape of molecular structures is poorly represented. To overcome this problem, fuzzy smoothing of descriptors is introduced.
Virtual screening calculates the dissimilarity between a pair of descriptors using various metrics. The use of metrics comprising numerous tunable parameters set by an optimization procedure can lead to 250-fold enrichment over random.
Examples and further possible applications will be discussed.
226th ACS National Meeting, New York, USA, Sept 7-11, 2003.
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By Zsuzsanna Szabó, Miklós Vargyas, Modest von Korff, Ferenc Csizmadia, György Pirok, Mathias Steger · August 2003
A large compound database is explored for structures that bare a similarity to a few given query structures, where the molecular similarity refers to the match of chemical, pharmacological and biological properties of two compounds.
In the starting part of the presentation the common marks, properties of two molecules are described. Molecular structures are encoded into molecular descriptors, e.g. fingerprints which can be handled numerically. That led to the method of virtual screening using these fingerprints. Fuzzy pharmacophore fingerprints offer a way to enhance the performance of screening and the introduction of tunable parameters in dissimilarity metrics can increase the performance too. In the second part of the presentation the optimalization of these parameters are discussed including the optimalization goal, the hypothesis, the examples of the hypothesis and the results. The pharmacophore perception is implemented within the ChemAxon’s JChem software tools.
Drug Discovery Technology, Boston, USA, August 10-15, 2003
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By Miklós Vargyas, Modest von Korff, György Pirok, Ferenc Csizmadia, Mathias Steger · August 2003
About 90% of drug targets cannot be crystallized. If the 3D structure of the active site is not available, a pharmacophore model is created. Such models are typically based on compounds that are known to bind to the target receptor. When creating pharmacophore models (either in 2D or in 3D) the pharmacophoric characteristic of known actives, as well as of candidates tested, have to be recognized.
The presentation gives an overview about the creation of pharmacophore models and perceptions. One possible approach to create pharmacophore models from 2D structures is to count frequencies of all atom-based pharmacophore point pairs with respect to their topological distance. On the other hand the rule based pharmacophore perception focuses on the molecules that are localized to moieties of the structure, defining whether the pharmacophore type of an atom will be a donor or an acceptor by rule. However, this perception has got two major problems: (1) large number of rules are needed to cope with exceptions; (2) different pH implies different rules. In the following section of the presentation the method of the hybrid approach for pharmacophore perception is thoroughly explained with its new rule-base and with results. The pharmacophore perception is implemented within ChemAxon’s JChem software tool.
Visit postBy György Pirok, Nóra Máté, Miklós Vargyas, Szilárd Dóránt, Ferenc Csizmadia · August 2003
With the advent of high throughput screening and combinatorialchemistry computer assisted chemistry plays an important role in selecting and designing new drug candidates. Pharmaceutical R&D demands methods for transforming huge numbers of chemical structures in a reasonable time.
Modeling chemical structures is a well established approach which has proved itself in practice, however there are many hazards on the road to virtual reaction processing. Specific virtual reactions work well with specific compounds but they are not usable for batch processing large molecule libraries. On the other hand, the application of generic reaction equations needs permanent manual control to eliminate chemically meaningless or not synthesizable products.
An ideal chemical transformation rule needs to be generic to apply to compound libraries yet specific so as to be able to process only chemically feasible transformations.
Visit postIn the field of computational chemistry it is usual to have only a partial set of structural information about compounds, like the connectivity or the formula. Individual studies can easily be performed using ‘human interfaces’ for building input structures.
However, automatic, ‘batch’ processes cannot be applied on a large number of molecules if they imply human intervention. Studies, like QSAR, pharamacophore analysis, reaction prediction might need full, complete 3D information for the compounds of interest. The widespread tools used for structure determination (force-fields or quantum chemical methods) even require a complete set of initial 3D coordinates.
Our approach intends on generating globally valid set of 3D coordinates for small and medium sized molecules, based on local structural criteria. Over against iterative, backtrack based structure predicting algorithms, our method is capable of satisfying partially inconsistent requirements. Such situations are common for structures holding polycyclic, rigid details.
Goals mentioned above can be achieved using coordinates interpreted in a space with a Minkowski metric. Our coordinate assignment process is divided into the following parts: (I) Automatic generation of distance criteria based on chemically relevant local properties, such as bond stretches, bond angles, dihedral angles, etc. (II) Multi-dimensional coordinate assignment which fulfills all the criteria. (III) Geometry optimization using a force field extended to the multi-dimensional Minkowski space. The optimization eliminates the over-3D components and yields the 3D coordinates.
The Role of Chemistry in the Evolution of Molecular Medicine, Szeged, Hungary, June 27-29, 2003
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The calculated pKa values could serve good interpretation for the selective reaction of different diamines in acidic medium. Summarizing the basic requirement for mono protection is 5 difference between the pKa values of the two amino groups.
The lower is the pKa of the free amine of the mono-Boc species the higher is the yield of the mono-boc product. Isolated diamines can be reacted according to the following rule: in acidic medium the lower in neutral medium the greater pKa valued nitrogen can be protected with acceptable selectivity. Alkyl chain longer than 3 carbons reduces the favorable neighborhood effect. Over 8 pKa difference value the amines can be reacted selectively in chemical reactions.
There are certain problems which this model overlooks:
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1. Stability of the protected amines vs. pH and temperature
2. Stability of the heterocyclic systems vs. pH and temperature
The bulky Boc O is very sensitive to the steric hindrance, which is confirmed by regioselectivity of the Boc-protection and the sensitivity of the reaction velocity to the steric hindrance.
Advancing Library Design and Organic Synthesis, La Jolla, California, February 24-27, 2003
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By András Borosy, Ferenc Csizmadia, András Volford · July 2001
To support clustering, new software called JKlustor has been developed as an add-on module for ChemAxon’s chemical database handling system, JChem. The application can generate 2D hashed fingerprints for molecules, but real number descriptors may also be used during the calculation. The clustering process applies a version of the Jarvis-Patrick method (Jarp), which is based on variable-length neighbor lists. In the case of fingerprint input, the measure of similarity is the Tanimoto coefficient. Another clustering module, applying Ward’s minimum variance method and using Murtagh’s reciprocal nearest neighbor (RNN) algorithm as a heuristic, is also introduced.
EuroCombi-1, First Symposium of the European Society of Combinatorial Science, Budapest, July 1-5, 2001
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By Ferenc Csizmadia · March 2000
A Java based development tool for building portable chemical information systems is presented. The system contains applets for constructing web-based interfaces and classes that add structure handling to relational databases. Custom applications built with JChem can combine SQL and structural queries.
Journal of Chemical Information and Computer Sciences, Volume 40, Issue 2 (March 27, 2000), Pages 323-324
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By Péter Csizmadia, Ferenc Csizmadia · August 1999
The presentation looks for the answers regarding new, efficient storage of molecular structures. The pdf file gives a short summary about the problem itself, it gathers the possible solutions and in the end of the presentation it will suggest one.
The internet is too slow to handle a large number of molecules in a minimum available time. The problem won’t be solved if the molecular data is stored in a standard format or in some proprietary binary format. The major solution that is introduced in this presentation is the compressed molfiles or csmole files. The second part of the presentation focuses on the searching in a network chemical database with the solutions of ChemAxon’s softwares that can import and export csmol files (MarvinSketch, MarvinView and JChem).
The 5th International Conference on Chemical Structures (5th ICCS), Noordwijkerhout, June 6-10, 1999
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By Péter Csizmadia · August 1999
This 1999 presentation gives an overall introduction to the ChemAxon’s Marvin family that was launched in those years. Marvin is an applet package for drawing and visualizing chemical structures and substructures and it can be used by anyone with a web browser.
The presentation mentions among the major advantages of the Marvin that it is faster than the similar applets because it is modularized, it can handle many file formats and it is highly configurable and controllable. After the general introduction to the Marvin two products of the family is described thoroughly. The first is the MarvinSketch which is a tool for drawing chemical structures. The other is MarvinView that is a 2D/3D viewer that can display a molecule, or many molecules in a table.
The 3rd International Electronic Conference on Synthetic Organic Chemistry (ECSOC-3)
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By Ferenc Csizmadia · June 1999
A Java based development tool for building portable chemical information systems is presented. The system contains applets for constructing web-based interfaces and classes that add structure handling to relational databases. Custom applications built with JChem can combine SQL and structural queries.
The 5th International Conference on Chemical Structures (5th ICCS), Noordwijkerhout, June 6-10, 1999
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By Ferenc Csizmadia, Ferenc Darvas · June 1999
This presentation describes the role of the complex chemical web applications through the example of the Chemazon, a webshop of a large amount of compounds produced by the ComGenex.
In the introduction the complex chemical web application’s technology is described: it combines the elements of web technology, database technology and chemical software technology. The complexity of the problem requires new directions from the ChemAxon: creating Java based softwares. It is compatible with almost all operation systems, web servers and database servers too.
The 5th International Conference on Chemical Structures (5th ICCS), Noordwijkerhout, June 6-10, 1999
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