Plaxco, Kevin W. and Mathiowetz, Alan M. and Goddard, William A., III (1989) Predictions of structural elements for the binding of Hin recombinase with the hix site of DNA. Proceedings of the National Academy of Sciences of the United States of America, 86 (24). pp. 9841-9845. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:PLApnas89
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Molecular dynamics simulations were coupled with experimental data from biochemistry and genetics to generate a theoretical structure for the binding domain of Hin recombinase complexed with the hix site of DNA. The theoretical model explains the observed sequence specificity of Hin recombinase and leads to a number of testable predictions concerning altered sequence selectivity for various mutants of protein and DNA. Combining molecular dynamics simulations with constraints based on current knowledge of protein structure leads to a theoretical structure of the binding domain of Hin recombinase with the hix site of DNA. The model offers a mechanistic explanation of the presently known characteristics of Hin and predicts the effects of specific mutations of both protein and DNA. The predictions can be tested by currently feasible experiments that should lead to refinements in and improvements on the current theoretical model. Because current experimental and theoretical methods are all limited to providing only partial information about protein-DNA interactions, we believe that this approach of basing molecular simulations on experimental knowledge and using the results of these simulations to design new, more precise experimental tests will be of general utility. These results provide additional evidence for the generality of the helix-turn-helix motif in DNA recognition and stabilization of proteins on DNA.
|Additional Information:||© 1989 by the National Academy of Sciences. Contributed by William A. Goddard III, September 25, 1989. We thank Professor Peter Dervan for helpful discussions. K.W.P. gratefully acknowledges support from the National Science Foundation in the form of a graduate fellowship. This project was initiated with support from Office of Naval Research/Defense Advanced Research Planning Agency and continued with support from Department of Energy-Energy Conversion and Utilization Technologies. The computations were carried out using BIOGRAF (from BioDesign) with modified routines for torque mechanics and for C0 constraints. The computers (Alliant FX8/8 and DEC VAX 8650) and graphics systems (Evans & Sutherland PS 330 and 390) were funded by Office of Naval Research/Defense Advanced Research Planning Agency, National Science Foundation-Materials Research Groups, Office of Naval Research-Special Research Opportunities, and Department of Energy-Energy Conversion and Utilization Technologies. This paper is Contribution 7771 from the Arthur Amos Noyes Laboratory of Chemical Physics. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
|Subject Keywords:||protein-DNA interactions; helix-turn-helix motif; molecular modeling; structure-function relationships; Salmonella typhimurium|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||04 Feb 2008|
|Last Modified:||26 Dec 2012 09:49|
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