TCB Publications - Abstract

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.

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