CoMFA and CoMSA approaches

Comparative molecular field analysis (CoMFA) is a widely used procedure for simulating the influence of the molecular shape when modeling steric (Lennard-Jones) and electrostatic (Coulomb) fields as being important intermolecular interactions that are involved in non-covalent ligand-receptor binding⁹⁰. Generally, the CoMFA approach is based on the assumption that a comparative analysis of the 3D patterns that are produced within the cubic mesh of points that encompasses aligned molecules using suitable probes can account for the differences in the binding affinities or the biological activity profiles for a congeneric series of compounds. In fact, the modeling efficiency of the electronic and steric potentials in the molecular environment is strictly dependent on the selection of a suitable atomic probe (usually z positively charged sp³ carbon atom) and the superimposition that is applied following the putative pharmacophore hypothesis. As a result, the distribution of the potential values on the mesh points relies on the molecular coordinates, which are valid factors that control the value of the atomic partial charges. The resulting potential energies at each lattice point can be illustrated graphically as a three-dimensional color contour pattern that indicates the spatial areas, where a steric hindrance and/or charged substituents enhances or diminishes the binding affinity⁹¹.

A self-organizing neural network (SOM) data processing was performed as described earlier⁹².