Computer-assisted modeling of antibody variable domains.
Antibody modeling is an interesting option to gain structure-function insights and to allow rational engineering of these molecules in the absence of experimental data. Among a diversity of algorithms, software packages, and specialized Web servers, the protocol described here presents the following main features: (1) nonautomatic modeling process guided by direct application of antibody modeling principles; (2) local generation of molecular models using free software which can be used in most common operational systems; and (3) the resulting model quality is comparable to models generated by Web servers which represent the current standard of antibody modeling. Briefly, hybrid models of heavy- and light-chain variable domains are separately built by grafting segments from homologous templates (framework regions and complementarity-determining regions). Next, hybrid models are mutated to comply with the target's sequence and associated by fitting into a template structure that closely matches the predicted packing angle for the target variable domains. After a few cycles of energy minimization the model can be submitted to CDR-H3 optimization or its quality can be directly assessed.
CEA ,iBiTecS, SIMOPRO, Gif-sur-Yvette, France. oscar.pereira-ramos@cea.fr
Oscar H P
OH
Ramos
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry*; D022801:Complementarity Determining Regions / Q000737:chemistry; D003198:Computer Simulation; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region