Thomas W. Lynch, Dorina Kosztin, Mark A. McLean, Klaus Schulten, and Stephen G.
Sligar.
Dissecting the molecular origins of protein-nucleic acid recognition:
Hydrostatic pressure and molecular dynamics.
Biophysical Journal, 82:93-98, 2002.
(PMC: 1302451)
LYNC2002
The fundamental processes by which proteins recognize and bind to nucleic acids are critical to understanding cellular function. To explore the factors involved in protein-DNA recognition, we used hydrostatic pressure to perturb the binding of the BamHI endonuclease to cognate DNA, both in experiment and in Molecular Dynamic (MD) simulations. A new technique of high pressure gel mobility shift analysis was employed to test the effects of elevated hydrostatic pressure on the binding of BamHI to its cognate recognition sequence. Upon application of a pressure of 500 bar, the equilibrium dissociation constant binding to the cognate site was found to increase nearly 10-fold. A challenge has been to link this type of pure thermodynamic measurement to functional events occurring at the molecular level. Thus, we used Molecular Dynamic simulations at both ambient and elevated pressures to reveal details of the direct and water-mediated interactions between BamHI and cognate DNA, which allow explanation of the effects of pressure on site-specificprotein-DNA binding and complex stability.
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.
