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Prediction of β‐sheet topology and disulfide bridges in polypeptides
Author(s) -
Klepeis J. L.,
Floudas C. A.
Publication year - 2002
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.10167
Subject(s) - disulfide bond , topology (electrical circuits) , computer science , chemistry , materials science , mathematics , combinatorics , biochemistry
An ab initio method has been developed to predict β architectures in polypeptides. The approach predicts the topology of β‐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 β‐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 β‐configuration. These (ILP) models can also predict a ranked ordered list of the best, second‐best, third‐best, etc., topologies of β‐sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential β‐sheet topologies folds (56 to 187 amino acids). © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 191–208, 2003