Similarity Analysis of Molecular Interaction Potential Distributions. The MIPSIM Software

Abstract

The Molecular Interaction Potentials (MIP) are standard tools for the comparison of series of compounds in the framework of Structure-Activity Relationship (SAR) studies [1]. These potentials are interaction energies between the considered compounds and relevant probes, which are usually computed in the points of a grid defined around the compounds (see Fig. 1). The historically most used probe is the proton, and the resulting MIP is called Molecular Electrostatic Potential (MEP). In previous works, we developed a computational system (MEPSIM) for the analysis and comparison of MEP distributions computed at the quantum mechanic level [2–5]. The two main modules of the MEPSIM software were MEPMIN and MEPCOMP. MEPMIN allowed the automatic characterisation of the MEP minima around a molecule (values, positions and geometric relationships). MEPCOMP dealt with the computation of a similarity measure (a Spearman rank correlation coefficient) between two MEP distributions. MEPCOMP also carried out a gradient-driven automatic search of the relative positions of the compared molecules that maximised the similarity measure. The present work presents an improved and extended version of the MEPSIM approach that, among other new features, allows the consideration of any MIP definition. This new software is called MIPSIM (Molecular Interaction Potentials SIMilarity analysis) [6].