Induced Fit and the Entropy of Structural Adaptation in the Complexation of CAP and Repressor with Cognate DNA Sequences

¹ Wesleyan University
² Northwestern University

^* To whom correspondence should be addressed. E-mail: dbeveridge{at}wesleyan.edu.

Submitted on September 30, 2004
Revised on December 17, 2004
Accepted on 8 February 2005

	Abstract

Molecular dynamics simulations of 5 ns on protein DNA complexes of Catabolite activator protein (CAP), repressor and on their corresponding uncomplexed protein and DNA are reported. These cases represent two extremes of DNA bending, with CAP DNA bent severely and the operator nearly straight when complexed with protein. The calculations were performed using the AMBER suite of programs and the parm94 force field, validated for these studies by good agreement with experimental NMR data on DNA. An explicit computational model of structural adaptation and computation of the quasi-harmonic entropy of association were obtained from the MD. The results indicate that, with respect to canonical B-form DNA, the extreme bending of the DNA in the complex with CAP is approximately 60% protein induced and 40% intrinsic to the sequence dependent structure of the free oligomer. The DNA in the complex is an energetically strained form, and the MD results are consistent with a "conformational capture" mechanism. The calculated quasiharmonic entropy change accounts for the entropy difference between the two cases. The calculated entropy was decomposed into contributions from protein adaptation, DNA adaptation and protein-DNA structural correlations. The origin of the entropy difference between CAP and repressor complexation arises more to the additional protein adaptation in the case of than to DNA bending and entropy contribution from DNA bending. The entropy arising from protein DNA cross correlations, a contribution not previously discussed, is surprisingly large.

Key Words: Configurational Entropy, DNA bending, Molecular dynamics simulation, Protein-DNA interactions, Quasi-Harmonic method

This article has been cited by other articles:

				R. Friedman, E. Nachliel, and M. Gutman Fatty Acid Binding Proteins: Same Structure but Different Binding Mechanisms? Molecular Dynamics Simulations of Intestinal Fatty Acid Binding Protein Biophys. J., March 1, 2006; 90(5): 1535 - 1545. [Abstract] [Full Text] [PDF]

				J. Magee and J. Warwicker Simulation of non-specific protein-mRNA interactions Nucleic Acids Res., November 27, 2005; 33(21): 6694 - 6699. [Abstract] [Full Text] [PDF]