Biologically enhanced sampling geometric docking and backbone flexibility treatment with multiconformational superposition

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2005-08, Vol.60 (2), p.319-323
• Main Authors: Ma, Xiao Hui, Li, Chun Hua, Shen, Long Zhu, Gong, Xin Qi, Chen, Wei Zu, Wang, Cun Xin
• Format: Article
• Language: English
• Subjects: active site; Algorithms; Animals; backbone flexibility; Bacterial Proteins - chemistry; Binding Sites; biologically enhanced sampling; Computational Biology - methods; Computer Simulation; Databases, Protein; Ligands; Macromolecular Substances; Models, Molecular; Models, Statistical; Molecular Conformation; multiconformational superposition; Protein Binding; Protein Conformation; Protein Folding; Protein Interaction Mapping - methods; Protein Structure, Tertiary; Proteomics - methods; Reproducibility of Results; Sequence Alignment; Software; Static Electricity; Structural Homology, Protein
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.20577

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 Å to 2.9 Å after performing multiconformational superposition. These results were obtained after the CAPRI prediction deadlines. Proteins 2005;60:319–323. © 2005 Wiley‐Liss, Inc.