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Structural refinement of protein segments containing secondary structure elements: Local sampling, knowledge‐based potentials, and clustering
Author(s) -
Zhu Jiang,
Xie Li,
Honig Barry
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.21085
Subject(s) - cluster analysis , dihedral angle , energy minimization , computer science , modular design , minification , protein secondary structure , protocol (science) , molecular dynamics , algorithm , protein structure prediction , data mining , protein structure , computational chemistry , artificial intelligence , physics , chemistry , molecule , medicine , hydrogen bond , alternative medicine , pathology , programming language , operating system , nuclear magnetic resonance , quantum mechanics
In this article, we present an iterative, modular optimization (IMO) protocol for the local structure refinement of protein segments containing secondary structure elements (SSEs). The protocol is based on three modules: a torsion‐space local sampling algorithm, a knowledge‐based potential, and a conformational clustering algorithm. Alternative methods are tested for each module in the protocol. For each segment, random initial conformations were constructed by perturbing the native dihedral angles of loops (and SSEs) of the segment to be refined while keeping the protein body fixed. Two refinement procedures based on molecular mechanics force fields — using either energy minimization or molecular dynamics — were also tested but were found to be less successful than the IMO protocol. We found that DFIRE is a particularly effective knowledge‐based potential and that clustering algorithms that are biased by the DFIRE energies improve the overall results. Results were further improved by adding an energy minimization step to the conformations generated with the IMO procedure, suggesting that hybrid strategies that combine both knowledge‐based and physical effective energy functions may prove to be particularly effective in future applications. Proteins 2006. © 2006 Wiley‐Liss, Inc.