PHARMACOPHORIC PATTERN-MATCHING IN PILES OF 3-DIMENSIONAL CHEMICAL STRUCTURES - COMPARISON OF CONFORMATIONAL-SEARCHING ALGORITHMS FOR FLEXIBLE SEARCHING

The conformational space of a flexible three-dimensional (3-D) molecule can be represented for searching purposes by a smoothed bounded-distance matrix. Such matrices provide an effective way of carrying out flexible searching, but search times can be much greater than with comparable rigid searches that take no account of conformational flexibility. The most time-consuming part of a flexible search is the final conformational search, and in this paper we compare the efficiency and the effectiveness of the distance geometry, systematic search, random search, genetic-algorithm, and directed-tweak methods for conformational searching. Experiments with sets of 1538 and 9886 flexible 3-D structures suggest that the most effective of these are the genetic-algorithm and directed-tweak methods, both of which are efficient enough to enable the searching of databases containing nontrivial numbers of flexible 3-D structures.