Probing antibody internal dynamics with fluorescence anisotropy and molecular dynamics simulations.

ABSTRACT: The solution dynamics of antibodies are critical to antibody function. We explore the internal solution dynamics of antibody molecules through the combination of time-resolved fluorescence anisotropy experiments on IgG1 with more than two microseconds of all-atom molecular dynamics (MD) simulations in explicit water, an order of magnitude more than in previous simulations. We analyze the correlated motions with a mutual information entropy quantity, and examine state transition rates in a Markov-state model, to give coarse-grained descriptors of the motions. Our MD simulations show that while there are many strongly correlated motions, antibodies are highly flexible, with F(ab) and F(c) domains constantly forming and breaking contacts, both polar and non-polar. We find that salt bridges br

SUBMITTER: Kortkhonjia E 

PROVIDER: S-EPMC3893241 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature