BIOPHYSICAL THEORY AND MODELING |
Interfacial water as a "hydration fingerprint" in the non-cognate complex of BamHI
Monika Fuxreiter 1*, Mihaly Mezei 2, István Simon 1 and Roman Osman 2
1 Institute of Enzymology
2 Department of Physiology and Biophysics, Mount Sinai School of Medicine
* To whom correspondence should be addressed. E-mail: monika{at}enzim.hu.
Submitted on March 21, 2005
Revised on April 21, 2005
Accepted on 10 May 2005
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Abstract |
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The molecular code of specific DNA recognition by proteins as a paradigm in molecular biology remains an unsolved puzzle primarily because of the subtle interplay between direct protein-DNA interaction and the indirect contribution from water and ions. Transformation of the non-specific, low affinity complex to a specific, high-affinity complex is accompanied by the release of interfacial water molecules. To provide insight into the conversion from the loose to the tight form we characterized the structure and energetics of water at the protein-DNA interface of the BamHI complex with a non-cognate sequence and in the specific complex. The fully hydrated models were produced with Grand Canonical Monte Carlo simulations. Proximity analysis shows that water distributions exhibit sequence dependent variations in both complexes, and in particular, in the non-cognate complex they discriminate between the correct and the star site. Variations in water distributions control the number of water molecules released from a given sequence upon transformation from the loose to the tight complex as well as the local entropy contribution to the binding free energy. We propose that interfacial waters can serve as a "hydration fingerprint" of a given DNA sequence.
Key Words:
Grand Canonical Monte Carlo simulations, nonspecific binding, protein-DNA recognition, proximity analysis, restriction enodnuclease, water release
