Probing antibody internal dynamics with fluorescence anisotropy and molecular dynamics simulations
Genre
Journal ArticleDate
2013-03-01Author
Kortkhonjia, EBrandman, R
Zhou, JZ
Voelz, VA
Chorny, I
Kabakoff, B
Patapoff, TW
Dill, KA
Swartz, TE
Subject
monoclonal antibodiessolution dynamics
molecular dynamics simulations
fluorescence anisotropy
therapeutic antibodies
Permanent link to this record
http://hdl.handle.net/20.500.12613/5587
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10.4161/mabs.23651Abstract
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 Fab and Fc domains constantly forming and breaking contacts, both polar and non-polar. We find that salt bridges break and reform, and not always with the same partners. While the MD simulations in explicit water give the right time scales for the motions, the simulated motions are about 3-fold faster than the experiments. Overall, the picture that emerges is that antibodies do not simply fluctuate around a single state of atomic contacts. Rather, in these large molecules, different atoms come in contact during different motions. © 2013 Landes Bioscience.Citation to related work
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http://dx.doi.org/10.34944/dspace/5569