Human IgG1 Fc pH-dependent optimization from a constant pH molecular dynamics simulation analysis.

ABSTRACT: The binding of IgG Fc with FcRn enables the long circulating half-life of IgG, where the Fc-FcRn complex interacts in a pH-dependent manner. This complex shows stronger interaction at pH ≤ 6.5 and weaker interaction at pH ≥ 7.4. The Fc-FcRn binding mechanism that promotes the long circulating half-life of IgG has prompted several IgG Fc-related mutational studies to focus on the pH-dependent Fc-FcRn complex interactions in order to improve the pharmacokinetic properties of Fc. Hence, in this study, we applied the in silico constant pH molecular dynamics (CpHMD) simulation approach to evaluate the human Fc-FcRn complex binding (pH 6.0) and dissociating (pH 7.5) mechanism at the molecular level. The analysis showed that the protonated state of the titratable residues changes from pH 6

SUBMITTER: Lim YY 

PROVIDER: S-EPMC9051383 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature