Computer implemented method for aligning flexible molecules by performing ensemble alignment in the internal coordinate space followed by rigid body alignment in cartesian space

摘要

A method is disclosed that overcomes the problem in the prior art of requiring the use of a template or base molecule in order to compare the three dimensional configurations of molecules. The disclosed method teaches that the requirement for a template can be eliminated by handling the components of configuration-conformation versus rotation and translation in three-dimensional space-separately. The internal coordinate (torsional) space is explored first using a multi-objective genetic algorithm to minimize strain while maximizing steric and pharmacophoric concordance. Optimal overlays in Cartesian space are then obtained by applying a 3D hypermolecule construction method that makes use of linear assignment to identify optimal feature correspondences between ligands.