Structural property calculations
Tools for compound geometry characterization
The field of molecular descriptors is strongly interdisciplinary and involves a mass of different theories. For the definition of molecular descriptors, knowledge of algebra, graph theory, information theory, computational chemistry, theories of organic reactivity and physical chemistry is usually required, although at different levels. For the use of the molecular descriptors, statistics, chemometrics, and the principles of the QSAR/QSPR approaches are necessary in addition to the specific knowledge of the problem. Moreover, programming, sophisticated software and hardware are often inseparable fellow-travelers of the researcher in this field. ChemAxon’s collection of structural property and molecular descriptor provide a powerful toolkit to calculate simple to complex structural characteristics.
Basic molecular values related to the elemental composition of the molecule are often used by synthetic or analytical chemists to characterize or identify molecules. ChemAxon’s Elemental Analysis plugin calculates several basic properties, such as molecular mass, formula, isotope formula and composition or atom count.
Map the hydrogen bond donor and acceptor sites
The Hydrogen Bond Donor-Acceptor plugin calculates atomic donor and acceptor sites for hydrogen bonding, which is a useful characteristic in defining ´drug likeness´. Atomic data and overall hydrogen bond donor and acceptor multiplicity can be predicted and displayed for the input molecule, or its dominant microspecies at a given pH.
Hückel Analysis plugin
The Hückel method is applied to predict localization energies L(+) and L(-) for electrophilic and nucleophilic attack at an aromatic center; lower L(+) or L(-) energy values mean more reactive atoms. As a consequence, the preferred atoms for an electrophilic or nucleophilic attack will be estimated according to their localization energies. The plugin also calculates the total π energy, the π electron density and the total electron density based on Hückel’s method.
Molar refractivity calculation
ChemAxon’s molar refractivity calculations are based on the atomic method proposed by Viswanadhan et al. Molar refractivity is strongly related to the volume of the molecules and to their polarizability. Therefore this measure is also related to the London dispersion forces which have important effect in drug-receptor interaction processes.
Get structural frameworks
Reduced structural representations of molecules play an important role in structure based compound comparison, including structural searches or clustering.
A commonly known example for these abstractions is the Bemis-Murcko framework calculation, which can be basis for structure based clustering processes.
Besides the Bemis-Murcko framework, the Structural Frameworks plugin can identify various substructural patterns, e.g. fused ring systems, largest fused ring systems or the complete set of smallest rings in a structure. The plugin also calculates the maximum common substructures of multiple molecules.
Calculate resonance structures
Lone pairs, radical electrons or formal charges of certain atoms in a molecule can migrate within a delocalized system. The results of this migration process are the resonance structures of the compound. ChemAxon’s resonance structure generator creates all resonance forms of a molecule, including the stable mesomer forms.
The Geometry bundle contains a set of calculations for various topology or 3D shape related properties of molecules, starting from basic topological properties to solvent accessible surface area.
Topology Analysis of molecules
Topological descriptors, simple atom or ring counts, other graph measures, and in a broader sense, graph-theoretical methods, have been widely applied for molecule characterization. ChemAxon offers an exhaustive set of Topological Descriptors that can be calculated within the Topology Analysis plugin.
This plugin provides characteristic values related to the geometrical structure of a molecule, such as minimal and maximal projection areas, projection radii, force field energies or van der Waals volume. The input can be the original molecular conformation or the lowest energy conformer of the input molecule.
Polar Surface Area (2D, TPSA)
Polar surface area (PSA) is known to show good correlation with the passive molecular transport through membranes and therefore allows estimation of transport properties for drugs. This descriptor is formed by polar atoms of the molecule. ChemAxon’s technology calculates the topological polar surface area (doi:10.1021/jm000942e), which is practically identical with the 3D PSA, while the calculation is approximately faster by two orders of magnitude. Therefore, this method is more suitable for fast bioavailability screening of large virtual libraries. The TPSA value can be calculated for both the neutral form and the major microspecies on a given pH.
Molecular Surface Area (3D, MSA)
If we consider the shape of atoms as spheres where the radii of the atoms are equal to the van der Waals’s radii, then we obtain the van der Waals surface area (VSA) of atoms. In a molecule, the VSA of an atom not hidden by another atom’s VSA is considered as the available VSA. The sum of available VSAs of atoms in a molecule is equal with the molecular VSA. Solvent molecules are also considered as a sphere which can contact with the molecular VSA.
The solvent accessible surface area (SASA) is equal to the surface area of a molecule that can be accessed by a solvent sphere. In the Molecular Surface Area plugin two types of approaches are available: van der Waals and solvent accessible area calculations.
Besides the total solvent accessible surface the plugin is capable of predicting the accessible positively and negatively charged sites, as well as the hydrophobic and polar sites (doi:10.1002/prot.10001).