Molecular dynamics simulation of the crystallizable fragment of IgG1-insights for the design of Fcabs.

ABSTRACT: An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule's conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect

SUBMITTER: Lai B 

PROVIDER: S-EPMC3907818 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature