An efficient algorithm for searching low-energy conformers of cyclic and acyclic molecules

Abstract

A set of strategies for exhaustively finding low-energy conformers of cyclic, acyclic or alicyclic molecules is presented. Starting from any conformation, local perturbation is systematically applied to all the flexible portions of the molecule in question to produce candidates of new conformation. The perturbations consist of flapping and/or flipping for endocyclic bonds and stepwise rotation for acyclic bonds. The conformations they produced are believed to lie close to the initial geometry in the conformational space. The global energy minimum (GEM) structure of the starting domain of conformational space can be quickly reached by always choosing the most stable of the conformers produced in the last perturbation cycle as the next initial structure. Once GEM of the domain is reached, the local perturbations direct the search gradually to higher and higher energy regions while exhaustively finding all the low-energy conformers therein. The variable search-limit strategy allows one to use unstable conformers as the initial structure for perturbation to ensure the exhaustiveness of the search in the low-energy region. By further increasing the search-limit, new domains of conformational space may be found. A program CONFLEX3 containing several additional strategies for improved performance has been tested for n-alkanes up to decane and cycloalkanes up to cyclododecane.