Prediction of β-sheet topology and disulfide bridges in polypeptides

✍ Scribed by J. L. Klepeis; C. A. Floudas

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 183 KB
• Volume: 24
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.10167

✦ Synopsis

An ab initio method has been developed to predict beta architectures in polypeptides. The approach predicts the topology of beta-sheets and disulfide bridges through a novel superstructure-based mathematical framework originally established for chemical process synthesis problems. Two types of superstructure are introduced, both of which emanate from the principle that hydrophobic interactions drive the formation of a beta-structure. The mathematical formulation of the problem results in a set of integer linear programming (ILP) problems that can be solved to global optimality to identify the optimal beta-configuration. These (ILP) models can also predict a ranked ordered list of the best, second-best, third-best, etc., topologies of beta-sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential beta-sheet topologies folds (56 to 187 amino acids).