Conformer Searching

Abstract

Conformer searching algorithms find minima in the Potential Energy Surface (PES) of a molecule, usually by following a torsion-driven approach. The minima represent conformers, which are interchangeable via free rotation around bonds. Conformers can be used as input to computational analyses, such as drug design, that can convey molecular reactivity, structure, and function. With an increasing number of rotatable bonds, finding optima in the PES becomes more complicated, as the dimensionality explodes. Kaplan is a new, free and open-source software package written by the author that uses a ring-based Evolutionary Algorithm (EA) to find conformers. The ring, which contains population members (or pmems), is designed to allow initial PES exploration, followed by exploitation of individual energy wells, such that the most energetically-favourable structures are returned. The strengths and weaknesses of existing publicly available conformer searchers are discussed, including Balloon, RDKit, Openbabel, Confab, Frog2, and Kaplan. Since RDKit is usually considered to be the best free package for conformer searching, its conformers for the amino acids were optimised using the MMFF94 forcefield and compared to the conformers generated by Kaplan. Amino acid conformers are well characterised, and provide insight for protein substructure. Of the 20 molecules, Kaplan found a lower energy minima for 12 of the structures and tied for 5 of them. Kaplan allows the user to specify which dihedrals (by atom indices) to optimise and angles to use, a feature that is not offered by other programs. The results from Kaplan were compared to a known dataset of amino acid conformers. Kaplan identified all 57 conformers of methionine to within 1.2Å, and found identical conformers for the 5 lowest-energy structures (i.e. within 0.083Å), following forcefield optimisation.