Protein-protein docking by simulating the process of association subject to biochemical constraints

We present a computational procedure for modeling protein–protein association and predicting the structures of protein–protein complexes. The initial sampling stage is based on an efficient Brownian dynamics algorithm that mimics the physical process of diffusional association. Relevant biochemical...

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Bibliographic Details
Published in:Proteins, structure, function, and bioinformatics Vol. 71; no. 4; pp. 1955 - 1969
Main Authors: Motiejunas, Domantas, Gabdoulline, Razif, Wang, Ting, Feldman-Salit, Anna, Johann, Tim, Winn, Peter J., Wade, Rebecca C.
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2008
Subjects:
Algorithms
Amino Acid Sequence
Animals
Biochemical Phenomena
Biochemistry
Brownian dynamics
clustering
Computational Biology - methods
Computer Simulation
Crystallography, X-Ray
Databases, Factual
Diffusion
encounter complex
flexible refinement
Fourier Analysis
Humans
Hydrogen Bonding
Models, Biological
molecular dynamics
Molecular Sequence Data
Osmolar Concentration
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
protein-protein association
protein-protein docking
Proteins - chemistry
Proteins - metabolism
Static Electricity
ISSN:0887-3585, 1097-0134, 1097-0134
Online Access:Get full text
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Summary:We present a computational procedure for modeling protein–protein association and predicting the structures of protein–protein complexes. The initial sampling stage is based on an efficient Brownian dynamics algorithm that mimics the physical process of diffusional association. Relevant biochemical data can be directly incorporated as distance constraints at this stage. The docked configurations are then grouped with a hierarchical clustering algorithm into ensembles that represent potential protein–protein encounter complexes. Flexible refinement of selected representative structures is done by molecular dynamics simulation. The protein–protein docking procedure was thoroughly tested on 10 structurally and functionally diverse protein–protein complexes. Starting from X‐ray crystal structures of the unbound proteins, in 9 out of 10 cases it yields structures of protein–protein complexes close to those determined experimentally with the percentage of correct contacts >30% and interface backbone RMSD <4 Å. Detailed examination of all the docking cases gives insights into important determinants of the performance of the computational approach in modeling protein–protein association and predicting of protein–protein complex structures. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Bibliography:BIOMS
ark:/67375/WNG-XDKP2ZSF-W
ArticleID:PROT21867
istex:E32464563977F50AC97791E3D3BFA6B0884CAB25
Klaus Tschira Foundation
BIOMS, University of Heidelberg, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany
Genome Center, University of California, Davis, 451 East Health Science Drive, 95616 Davis CA, USA
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0887-3585
1097-0134
1097-0134
DOI:10.1002/prot.21867