Conformational perturbation of peptides in presence of polar organic solvents

Abstract

The critical role played by solvent environment in maintaining the conformational integrity of peptides and proteins is accepted without question. Numerous experiments have suggested that perturbing the solvent environment of peptides and proteins by the addition of polar organic solvents have important consequences for the conformation of these molecules. However, experimental studies of such perturbations often report different kinds of effects depending on the solvent used and/or the sequence/structure of the molecule under study. In this work we report a simulation based comparative study on the effects of adding two common organic solvents viz. Dimethyl sulfoxide (DMSO) and Acetonitrile (MeCN) on the dynamical conformation of a test peptide Ace-Gly-X-Gly-Nme where X is any amino acid. Our studies identify important differences in peptide solvation by these two solvents, which we attempt to correlate with the kinetic stability of the conformation, as well as the identity of the central 'X' residue in the test peptide.

Keywords: Delaunay tessellation; Molecular dynamics simulations; Peptide conformation; Preferential binding; Preferential hydration; Statistical geometry.