A soft docking algorithm for predicting the structure of antibody-antigen complexes.
An efficient soft docking algorithm is described for predicting the mode of binding between an antibody and its antigen based on the three-dimensional structures of the molecules. The basic tools are the "simplified protein" model and the docking algorithm of Wodak and Janin. The side-chain flexibility of Arg, Lys, Asp, Glu, and Met residues on the protein surface is taken into account. A combined filtering technique is used to select candidate binding modes. After energy minimization, we calculate a scoring function, which includes electrostatic and desolvation energy terms. This procedure was applied to targets 04, 05, and 06 of CAPRI, which are complexes of three different camelid antibody VHH variable domains with pig alpha-amylase. For target 06, two native-like structures with a root-mean-square deviation < 4.0 A relative to the X-ray structure were found within the five top ranking structures. For targets 04 and 05, our procedure produced models where more than half of the antigen residues forming the epitope were correctly predicted, albeit with a wrong VHH domain orientation. Thus, our soft docking algorithm is a promising tool for predicting antibody-antigen recognition.
Li
Chun Hua
CH
College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China.
Ma
Xiao Hui
XH
Chen
Wei Zu
WZ
Wang
Cun Xin
CX
D000465:Algorithms; D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D046911:Macromolecular Substances; D008958:Models, Molecular; D011485:Protein Binding; D025941:Protein Interaction Mapping; D000516:alpha-Amylases / Q000737:chemistry / Q000276:immunology
D000906:Antibodies; D000941:Antigens; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D046911:Macromolecular Substances; D000516:alpha-Amylases