Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics

J. Zimmermann, E.L. Oakman, I.F. Thorpe, X. Shi, P. Abbyad, C.L. Brooks, III, S.G. Boxer, F.E. Romesberg, Proc. Natl. Acad. Sci. USA (2006) 103:13722-13727.
pubpic2006zimmermannWe report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein.

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