Flexibility and conformational entropy in protein-protein binding

被引:123
作者
Grünberg, R
Nilges, M
Leckner, J
机构
[1] Chalmers Univ Technol, Dept Chem & Biol Engn Mol Biotechnol, SE-40530 Gothenburg, Sweden
[2] Inst Pasteur, CNRS, URA 2185, Unite Bioinformat Struct, F-75015 Paris, France
关键词
D O I
10.1016/j.str.2006.01.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To better understand the interplay between protein-protein binding and protein dynamics, we analyzed molecular dynamics simulations of 17 protein-protein complexes and their unbound components. Complex formation does not restrict the conformational freedom of the partner proteins as a whole, but, rather, it leads to a redistribution of dynamics. We calculate the change in conformational entropy for seven complexes with quasilharmonic analysis. We see significant loss, but also increased or unchanged conformational entropy. Where comparison is possible, the results are consistent with experimental data. However, stringent error estimates based on multiple independent simulations reveal large uncertainties that are usually overlooked. We observe substantial gains of pseudo entropy in individual partner proteins, and we observe that all complexes retain residual stabilizing intermolecular motions. Consequently, protein flexibility has an important influence on the thermodynamics of binding and may disfavor as well as favor association. These results support a recently proposed unified model for flexible protein-protein association.
引用
收藏
页码:683 / 693
页数:11
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