Induced fit and the entropy of structural adaptation in the complexation of CAP and lambda-repressor with cognate DNA sequences.

Abstract:

:Molecular dynamics (MD) simulations of 5 ns on protein-DNA complexes of catabolite-activator protein (CAP), lambda-repressor, and their corresponding uncomplexed protein and DNA, are reported. These cases represent two extremes of DNA bending, with CAP DNA bent severely and the lambda-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 nuclear magnetic resonance data on DNA. An explicit computational model of structural adaptation and computation of the quasiharmonic 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 lambda-repressor complexation arises more from the additional protein adaptation in the case of lambda, 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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Dixit SB,Andrews DQ,Beveridge DL

doi

10.1529/biophysj.104.053843

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

3147-57

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(05)73367-1

journal_volume

88

pub_type

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