Flexibility and conformational entropy in protein-protein binding.
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 quasiharmonic 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.
Grünberg
Raik
R
Unité de Bioinformatique Structurale, CNRS URA 2185, Institut Pasteur, 25-28 rue du docteur Roux, F-75015 Paris, France.
Nilges
Michael
M
Leckner
Johan
J
D000818:Animals; D001665:Binding Sites; D019277:Entropy; D004798:Enzymes / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018583:Pliability; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics; D013997:Time Factors
D004798:Enzymes; D008024:Ligands; D011506:Proteins