Sergei Izrailev, Sergey Stepaniants, Manel Balsera, Yoshi Oono, and Klaus
Schulten.
Molecular dynamics study of unbinding of the avidin-biotin complex.
Biophysical Journal, 72:1568-1581, 1997.
(PMC: 1184352)
IZRA97
We report molecular dynamics simulations which induce, over periods of 40-500 ps, the unbinding of biotin from avidin by means of external harmonic forces with force constraints close to those of AFM cantilevers. The applied forces are sufficiently large to reduce the overall binding energy enough to yield unbinding within the measurement time. Our study complements earlier work on biotin-streptavidin that employed a much larger harmonic force constant. The simulations reveal a variety of unbinding pathways, the role of key residues contributing to adhesion as well as the spatial range over which avidin binds biotin. In contrast to the previous studies, the calculated rupture forces exceed by far those observed. We demonstrate, in the framework of models expressed in terms of one-dimensional Langevin equations with a schematic binding potential, the associated Smoluchowski equations, and the theory of first passage times, that picosecond to nanosecond simulation of ligand unbinding requires such strong forces that the resulting protein-ligand motion proceeds far from the thermally activated regime of millisecond AFM experiments, and that simulated unbinding cannot be readily extrapolated to the experimentally observed rupture.
Download Full Text
The manuscripts available on our site are provided for your personal
use only and may not be retransmitted or redistributed without written
permissions from the paper's publisher and author. You may not upload any
of this site's material to any public server, on-line service, network, or
bulletin board without prior written permission from the publisher and
author. You may not make copies for any commercial purpose. Reproduction
or storage of materials retrieved from this web site is subject to the
U.S. Copyright Act of 1976, Title 17 U.S.C.
Download full text: PDF ( 1.8MB), PS (944.1KB), Journal
