Biologically enhanced sampling geometric docking and backbone flexibility treatment with multiconformational superposition.
An efficient biologically enhanced sampling geometric docking method is presented based on the FTDock algorithm to predict the protein-protein binding modes. The active site data from different sources, such as biochemical and biophysical experiments or theoretical analyses of sequence data, can be incorporated in the rotation-translation scan. When discretizing a protein onto a 3-dimensional (3D) grid, a zero value is given to grid points outside a sphere centered on the geometric center of specified residues. In this way, docking solutions are biased toward modes where the interface region is inside the sphere. We also adopt a multiconformational superposition scheme to represent backbone flexibility in the proteins. When these procedures were applied to the targets of CAPRI, a larger number of hits and smaller ligand root-mean-square deviations (RMSDs) were obtained at the conformational search stage in all cases, and especially Target 19. With Target 18, only 1 near-native structure was retained by the biologically enhanced sampling geometric docking method, but this number increased to 53 and the least ligand RMSD decreased from 8.1 A to 2.9 A after performing multiconformational superposition. These results were obtained after the CAPRI prediction deadlines.
Ma
Xiao Hui
XH
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
Li
Chun Hua
CH
Shen
Long Zhu
LZ
Gong
Xin Qi
XQ
Chen
Wei Zu
WZ
Wang
Cun Xin
CX
D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D008024:Ligands; D046911:Macromolecular Substances; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012984:Software; D055672:Static Electricity; D040681:Structural Homology, Protein
D001426:Bacterial Proteins; D008024:Ligands; D046911:Macromolecular Substances