Methods for the homology modeling of antibody variable regions

Methods Mol Biol. 2012:857:301-11. doi: 10.1007/978-1-61779-588-6_13.

Abstract

Antibodies are one of the critical molecules of our immune system and are unique in their enormous diversity required for recognizing various antigens. Antibodies are protein molecules and their antigen interacting region, the fragment variable (F (V)), is typically composed of a light (V (L)) and heavy (V (H)) chain. In particular, three loops each at the tip of the V (L) and the V (H), known as the complementarity determining region (CDR) loops, are responsible for binding to the antigen. While the framework regions of the V (L) and V (H) are relatively constant across the entire repertoire of antibodies, the conformation of the CDR loops varies extensively to enable the antibody to recognize different antigens. Three-dimensional structures of antibodies illustrating the V (L)-V (H) relative orientation and the CDR conformations are needed to gain insight into antibody stability, immunogenicity, and antibody-antigen interactions. Computational modeling provides a fast and inexpensive route for generating antibody structural models. This chapter highlights the various features crucial for creating a successful antibody homology model.

MeSH terms

  • Animals
  • Computer Simulation
  • Humans
  • Immunoglobulin Variable Region / chemistry*
  • Models, Molecular
  • Protein Structure, Secondary
  • Structural Homology, Protein*

Substances

  • Immunoglobulin Variable Region