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High‐resolution prediction of protein helix positions and orientations
Author(s) -
Li Xin,
Jacobson Matthew P.,
Friesner Richard A.
Publication year - 2004
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.20014
Subject(s) - helix (gastropod) , globular protein , force field (fiction) , protein structure prediction , protein folding , ab initio , loop modeling , crystallography , folding (dsp implementation) , algorithm , protein structure , computer science , physics , chemistry , artificial intelligence , biology , engineering , ecology , snail , electrical engineering , nuclear magnetic resonance , quantum mechanics
We have developed a new method for predicting helix positions in globular proteins that is intended primarily for comparative modeling and other applications where high precision is required. Unlike helix packing algorithms designed for ab initio folding, we assume that knowledge is available about the qualitative placement of all helices. However, even among homologous proteins, the corresponding helices can demonstrate substantial differences in positions and orientations, and for this reason, improperly positioned helices can contribute significantly to the overall backbone root‐mean‐square deviation (RMSD) of comparative models. A helix packing algorithm for use in comparative modeling must obtain high precision to be useful, and for this reason we utilize an all‐atom protein force field (OPLS) and a Generalized Born continuum solvent model. To reduce the computational expense associated with using a detailed, physics‐based energy function, we have developed new hierarchical and multiscale algorithms for sampling the helices and flanking loops. We validate the method using a test suite of 33 cases, which are drawn from a diverse set of high‐resolution crystal structures. The helix positions are reproduced with an average backbone RMSD of 0.6 Å, while the average backbone RMSD of the complete loop–helix–loop region (i.e., the helix with the surrounding loops, which are also repredicted) is 1.3 Å. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.