Markush structures – From molecules towards patents 2009 ICIC presentationPresentation by Szabolcs Csepregi, Nóra Máté, Róbert Wagner, Szilárd Dóránt, Erika Biró, Tamás Csizmadia, Tim Dudgeon, Ferenc Csizmadia · 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.
Full abstractThe 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.
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Representation, searching & enumeration of Markush structures - from molecules towards patents - 2009 updatePresentation by Erika Biró, Ferenc Csizmadia, Nóra Máté, Róbert Wagner, Szabolcs Csepregi, Szilárd Dóránt, Tamás Csizmadia · 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.
Full abstractThe 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.
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Flexible 3D alignment and its application in virtual screeningPresentation by 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.
Full abstractMost 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.
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Instant JChemPresentation by Tim Dudgeon · March 2009
Instant 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.
Full abstract 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
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Pipelining ChemAxonPresentation by et al, Szilárd Dóránt · December 2008
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.
Full abstractThe 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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Migration from ISIS environmentsPresentation by et al, Szabolcs Csepregi · November 2008
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.
Full abstractThe 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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ChemAxon for DevelopersPresentation by Ferenc Csizmadia · November 2008
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.
Full abstractThe 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 softwares. For example the Pipeline Pilot, KNIME, Spotfire, Aureus and Integrity are mentioned among the most important vendors.
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Alternatives to MDL® CheshirePresentation by György Pirok · November 2008
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.
Full abstractIn 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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Working with IUPAC names using ChemAxon toolsPresentation 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).
Full abstractSuch 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
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Representation, searching and enumeration of Markush structures - from molecules towards patentsPresentation by Szabolcs Csepregi, Nóra Máté, Szilárd Dóránt, Erika Biró, Tamás Csizmazia, 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.
Full abstractThe 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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Chemical Terms - Functions for CheminformaticsPresentation by 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.
Full abstractMany 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
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What's new for Pipeline PilotPresentation by Larry Norder, Szilárd Dóránt · March 2008
Pipeline 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.
Full abstractAfter 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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Tautomer generation. pKa based dominance conditions for generating dominant tautomersPresentation 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.
Full abstractIn 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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IUPAC name generation; challenges and evaluationPresentation 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.
Full abstractThe 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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A method for calculating the pKa values of small and large moleculesPresentation 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.
Full abstractThe 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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Chemical Terms, a Language for CheminformaticsPresentation 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”.
Full abstractOn 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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Advanced Automatic Generation of 3D Molecular StructuresPresentation by 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.
Full abstractMoreover, 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.
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3D structure prediction and conformational analysisPresentation by Gábor Imre, Ödön Farkas · June 2005
Numerous 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.
Full abstractOur 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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Prediction of dissociation constant using microconstantsPresentation 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.
Full abstractThe 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
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Prediction of distribution coefficient using microconstantsPresentation by 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.
Full abstractThe 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
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