title: Protein-protein docking by simulating the process of association subject to biochemical constraints.
abstract: 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 A. 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.
authors.affiliation: EML Research gGmbH, Schloss-Wolfsbrunnenweg 33, 69118 Heidelberg, Germany.
authors.forename: Domantas
authors.initials: D
authors.lastname: Motiejunas
authors.forename: Razif
authors.initials: R
authors.lastname: Gabdoulline
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Anna
authors.initials: A
authors.lastname: Feldman-Salit
authors.forename: Tim
authors.initials: T
authors.lastname: Johann
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Winn
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Wade
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D004058:Diffusion; D005583:Fourier Analysis; D006801:Humans; D006860:Hydrogen Bonding; D008954:Models, Biological; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D011506:Proteins