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Optimized grid‐based protein–protein docking as a global search tool followed by incorporating experimentally derivable restraints
Author(s) -
Huang Wei,
Liu Haiyan
Publication year - 2012
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.23223
Subject(s) - docking (animal) , fast fourier transform , computer science , macromolecular docking , searching the conformational space for docking , grid , computation , algorithm , protein structure , chemistry , molecular dynamics , computational chemistry , mathematics , medicine , biochemistry , nursing , geometry
Unbound protein docking, or the computational prediction of the structure of a protein complex from the structures of its separated components, is of importance but still challenging. A practical approach toward reliable results for unbound docking is to incorporate experimentally derived information with computation. To this end, truly systematic search of the global docking space is desirable. The fast Fourier transform (FFT) docking is a systematic search method with high computational efficiency. However, by using FFT to perform unbound docking, possible conformational changes upon binding must be treated implicitly. To better accommodate the implicit treatment of conformational flexibility, we develop a rational approach to optimize “softened” parameters for FFT docking. In connection with the increased “softness” of the parameters in this global search step, we use a revised rule to select candidate models from the search results. For complexes designated as of low and medium difficulty for unbound docking, these adaptations of the original FTDOCK program lead to substantial improvements of the global search results. Finally, we show that models resulted from FFT‐based global search can be further filtered with restraints derivable from nuclear magnetic resonance (NMR) chemical shift perturbation or mutagenesis experiments, leading to a small set of models that can be feasibly refined and evaluated using computationally more expensive methods and that still include high‐ranking near‐native conformations. Proteins 2011. © 2012 Wiley Periodicals, Inc.