Antibodies are globular proteins composed of two heterodimers with each set containing a light chain (VL) and a heavy chain (VH). The binding to antigen is in most antibodies facilitated by six loops, three originating from the VL domain, termed L1, L2 and L3, and three from the VH domain, termed H1, H2 and H3. Due to their modular composition and high target specificity antibodies have become increasingly attractive for use as therapeutics. Antibody Homology Modeling techniques have often been applied in the context of engineering therapeutically more effective antibodies. Here, we demonstrate a collection of procedures that facilitate efficient antibody homology modeling. The application has flexible components allowing integration of various work-flows associated with this specific form of modeling. The routines take into account the subdomain composition of antibodies when searching for template candidates and building models. A knowledge-based modeling approach is applied with an underlying database of antibody structures originating from the Protein Data Bank (PDB). A specially designed loop grafting routine allows for generation of xenogeneic antibody models.

Methodologies for efficient antibody homology modeling

241st National Meeting (2011)

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