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

✍ Scribed by Tran Trung Tran; Herbert Treutlein; Antony W. Burgess

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 334 KB
• Volume: 22
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.1062

✦ Synopsis

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 sp^2^ 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 charges and dipoles. The van der Waals parameters were obtained by fitting to high‐resolution crystallographic data, and the nonbonded parameters were verified by comparing with experimentally derived lattice energy. The bonded parameters were derived by least‐square fits to the ab initio calculated energy surfaces, i.e., conformational energy as well as their first and second derivatives of seven model thioamide molecules. When the sp^2^ sulfur parameters were tested on a set of seven X‐ray crystallographic structures from the Cambridge Structural Database, they satisfactorily reproduced the bond lengths, bond angles, torsional angles, and nonbonded distances of all the crystal structures. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1010–1025, 2001