Flexibility and conformational entropy in protein-protein binding

Structure
Raik GrünbergJohan Leckner

Abstract

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.

References

Oct 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·D Lancet, I Pecht
Dec 2, 1975·Biochemistry·R H AustinI C Gunsalus
Oct 1, 1992·Proteins·H L Gordon, R L Somorjai
Oct 1, 1989·Protein Engineering·A V Finkelstein, J Janin
Jan 1, 1988·Advances in Protein Chemistry·P L Privalov, S J Gill
Jul 7, 1995·Journal of Molecular Biology·R M Jackson, M J Sternberg
Jan 1, 1995·Proteins·J Janin
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·J Foote, C Milstein
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·T N BhatR J Poljak
Apr 1, 1997·Current Opinion in Structural Biology·G P Brady, K A Sharp
Mar 28, 1998·The Journal of Experimental Medicine·M A HolmesJ Foote
Apr 16, 1998·Protein Science : a Publication of the Protein Society·L S CavesM Karplus
Sep 10, 1998·Nature Structural Biology·H Frauenfelder, D T Leeson
Feb 2, 1999·Journal of Molecular Biology·L Lo ConteJ Janin
Jun 1, 1999·FEBS Letters·C BergerH R Bosshard
Dec 3, 1999·Nature Structural Biology·J D Forman-Kay
Dec 3, 1999·Nature Structural Biology·L ZídekM J Stone
Mar 8, 2000·Biochemistry·B VerganiM Chabbert
Mar 30, 2000·Protein Science : a Publication of the Protein Society·S KumarR Nussinov
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·B A ShoemakerP G Wolynes
Jul 21, 2001·Biophysical Journal·S Y Noskov, C Lim
Nov 8, 2001·Journal of Molecular Biology·C WangL K Nicholson
Feb 27, 2003·The Journal of Biological Chemistry·Rosa FayosPatricia A Jennings
Mar 14, 2003·Journal of Molecular Biology·S ArumugamSteven R Van Doren
Mar 21, 2003·Biophysical Chemistry·Jack Kyte
Apr 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christian F W BeckerMartin Engelhard
May 3, 2003·Current Opinion in Structural Biology·S GnanakaranAngel E García
May 22, 2003·Journal of Computational Chemistry·Kristin L MeagherHeather A Carlson
May 1, 1965·Journal of Molecular Biology·J MONODJ P CHANGEUX

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Citations

Nov 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Antoine TalyJean-Pierre Changeux
Jul 8, 2011·Journal of Computer-aided Molecular Design·Jožica DolencWilfred F van Gunsteren
Oct 5, 2010·Nature Chemical Biology·Larry R MastersonGianluigi Veglia
Jul 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sara E DobbinsMichael J E Sternberg
Apr 29, 2009·Journal of the American Chemical Society·Anthony MansonVincent J Hilser
Apr 14, 2010·Nucleic Acids Research·Raik Grünberg, Luis Serrano
May 25, 2011·Molecular and Cellular Biology·Chih-Hong ChenCarol Beth Post
Jul 5, 2007·European Biophysics Journal : EBJ·Antoine Taly
Mar 25, 2009·Cellular and Molecular Life Sciences : CMLS·Kaare TeilumBirthe B Kragelund
Sep 25, 2008·Quarterly Reviews of Biophysics·Joël JaninPinak Chakrabarti
Jan 2, 2014·Journal of Molecular Biology·Jaafar N HaidarZhiping Weng
May 1, 2016·Protein Engineering, Design & Selection : PEDS·Asli Yenenler, Osman Ugur Sezerman
Jul 11, 2016·The Journal of Chemical Physics·J Copperman, M G Guenza
Jul 16, 2016·Chembiochem : a European Journal of Chemical Biology·Gyula PálfyAndrea Bodor
Aug 26, 2016·Journal of Biomolecular Structure & Dynamics·Richa Anand, B S Sanjeev
Oct 24, 2007·The Journal of Chemical Physics·David D L MinhJ Andrew McCammon
Mar 16, 2017·Biophysical Journal·Debipreeta BhowmikDipankar Chatterji
Jul 1, 2017·Journal of Chemical Information and Modeling·Duc D NguyenGuo-Wei Wei
Dec 9, 2017·Journal of Molecular Recognition : JMR·Meryl WangBuyong Ma
Oct 24, 2017·Soft Matter·Fernando Vargas-LaraJack F Douglas
Jul 2, 2015·Organic & Biomolecular Chemistry·Hongmei SunChristopher A Hunter
Jul 19, 2012·Proteins·Noël Malod-DogninFrédéric Cazals
Oct 21, 2018·Proceedings of the National Academy of Sciences of the United States of America·Marcelo E GuerinDavid Giganti
Sep 13, 2018·Journal of Cellular Biochemistry·G R C PereiraJ F De Mesquita
Jul 20, 2007·Nature·Kendra King FrederickA Joshua Wand
May 23, 2008·Journal of Molecular Recognition : JMR·Kathryn M ArmstrongBrian M Baker
Apr 22, 2010·Proteins·Dana Movshovitz-AttiasOra Schueler-Furman

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