Statistical Distribution of Molecular Conformations and Its Application in QSAR Research

Abstract

The CSD (Conformation Statistical Distribution) method is presented. It carries out a very fast scanning of the whole conformational hypersurface of a molecule having n internal rotational degrees of freedom, through the calculation of the nonbonded intramolecular energy for each point of a n-dimensional homogeneous grid in the surface- The method allows then to calculate both the probabilities (according to Boltzmann’s statistics) with which the molecule assumes its proper energetically possible conformations and the statistical weights of the various conformational minima in which the molecule can be found. An averaged picture of the conformational possibilities of a bioactive molecule while approaching the receptor site can thus be given.

Some examples show the use of such a weighted mean in QSAR research aimed at the determination of molecular descriptors (conformarional freedom, molecular shape, total dipole moment and other steric and electronic features) related to activities in series of bioactive compounds.