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Novel approach for α‐helical topology prediction in globular proteins: Generation of interhelical restraints
Author(s) -
McAllister S. R.,
Mickus B. E.,
Klepeis J. L.,
Floudas C. A.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21095
Subject(s) - protein folding , globular protein , folding (dsp implementation) , protein structure prediction , topology (electrical circuits) , lattice protein , protein design , protein structure , crystallography , computer science , chemistry , physics , mathematics , combinatorics , engineering , biochemistry , electrical engineering
The protein folding problem represents one of the most challenging problems in computational biology. Distance constraints and topology predictions can be highly useful for the folding problem in reducing the conformational space that must be searched by deterministic algorithms to find a protein structure of minimum conformational energy. We present a novel optimization framework for predicting topological contacts and generating interhelical distance restraints between hydrophobic residues in α‐helical globular proteins. It should be emphasized that since the model does not make assumptions about the form of the helices, it is applicable to all α‐helical proteins, including helices with kinks and irregular helices. This model aims at enhancing the ASTRO‐FOLD protein folding approach of Klepeis and Floudas (Journal of Computational Chemistry 2003;24:191–208), which finds the structure of global minimum conformational energy via a constrained nonlinear optimization problem. The proposed topology prediction model was evaluated on 26 α‐helical proteins ranging from 2 to 8 helices and 35 to 159 residues, and the best identified average interhelical distances corresponding to the predicted contacts fell below 11 Å in all 26 of these systems. Given the positive results of applying the model to several protein systems, the importance of interhelical hydrophobic‐to‐hydrophobic contacts in determining the folding of α‐helical globular proteins is highlighted. Proteins 2006. © 2006 Wiley‐Liss, Inc.