IgG1 and IgG4 antibodies sample initial structure dependent local conformational states and exhibit non-identical Fab dynamics.

ABSTRACT: We have investigated the dynamics of two [Formula: see text]-immunoglobulin molecules, IgG1 and IgG4, using long all atom molecular dynamics simulations. We first show that the de novo structures of IgG1 and IgG4 predicted using AlphaFold, with no interactions between the fragment crystallizable (Fc) domain and the antigen fragment binding domain (Fab), eventually relaxes to a state with persistent Fc-Fab interactions that mirrors experimentally resolved structures. We quantified the conformational space sampled by antibody trajectories spawned from six different initial structures and show that the individual trajectories only sample states bound by a local minimum and display very little mixing in their conformational states. Furthermore, the dynamics of the individual Fab domains are st

SUBMITTER: Natesan R 

PROVIDER: S-EPMC10036467 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature