Conformational analysis of thiopeptides: Derivation of sp2 sulfur parameters for the CFF91 force field

Abstract

When a sulfur atom is used to substitute for the oxygen in peptide bonds, its bulkiness should restrict the conformational space available to an amino acid. This conformational restriction as well as the ability to confer resistance to enzymatic degradation in the body means that thio-substituted amino acids are potentially useful building blocks for drug design. To simulate the effects of thio substitution, force field parameters for sp2 sulfur are required. In this article, parameters for the thioamide group have been derived for the molecular mechanics CFF91 force field (available at http://www.ludwig.edu.au/archive/tran). The bond increment charges were obtained by fitting to ab initio c..