Conformational Coverage by a Genetic Algorithm

Abstract

A new approach for coverage of the conformational space by a limited number of conformers is proposed. Instead of using a systematic search whose time complexity increases exponentially with degrees of freedom, a genetic algorithm (GA) is employed to minimize 3D similarity among the conformers generated. This makes the problem computationally feasible even for large, flexible molecules. The 3D similarity of a pair of conformers is assumed to be reciprocal to the root-mean-square (rms) distance between identical atomic sites in an alignment providing its minimum. Thus, in contrast to traditional GA, the fitness of a conformer is not quantified individually but only in conjunction with the population it belongs to. The approach handles the following stereochemical and conformational degrees of freedom: rotation around acyclic single and double bonds, inversion of stereocenters, flip of free corners in saturated rings, and reflection of pyramids on the junction of two or three saturated rings. The latter tw...