PMID: 9533625Apr 9, 1998Paper

Electrostatic contributions to protein-protein binding affinities: application to Rap/Raf interaction

Proteins
I MueggeA Warshel

Abstract

The challenge of evaluating absolute binding free energies of protein-protein complexes is addressed using the scaled Protein Dipoles Langevin Dipoles (PDLD/S) model in combination with the Linear Response Approximation (LRA). This is done by taking the complex between Rap1A (Rap) and the p21ras binding domain of c-Raf (Raf-RBD) (Nassar et al., Nature 375:554-560, 1995) as a model system. Several formulations and different thermodynamic cycles are explored taking advantage of the LRA method and considering the protein reorganization during complex formation. The performance of different approximations is examined by comparing the calculated and observed absolute binding energies for the native complex and some of its mutants. The evaluation of the contributions of individual residues to the binding free energy, which is referred to here as group contributions is also examined. Special attention is paid to the role of the "dielectric constant," epsilon(in) which is in fact a scaling factor that represents the contributions that are treated implicitly. It is found that explicit consideration of protein relaxation is crucial for obtaining reasonable results with small values of epsilon(in), but it is also found that such a treatme...Continue Reading

References

Aug 28, 1975·Nature·C Chothia, J Janin
Mar 15, 1992·European Journal of Biochemistry·W F van Gunsteren, A E Mark
Jan 1, 1991·Annual Review of Biophysics and Biophysical Chemistry·A Warshel, J Aqvist
Jan 1, 1990·Annual Review of Biophysics and Biophysical Chemistry·K A Sharp, B Honig
Jan 1, 1987·Annual Review of Biochemistry·M Barbacid
Aug 1, 1984·Quarterly Reviews of Biophysics·A Warshel, S T Russell
Aug 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A WarshelA K Churg
Jan 1, 1995·Proteins·J Janin
May 6, 1994·Journal of Molecular Biology·J AntosiewiczM K Gilson
Mar 1, 1994·Protein Engineering·J AqvistJ E Samuelsson
Aug 1, 1996·Nature Structural Biology·N NassarA Wittinghofer

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Citations

Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lubos VrbkaPavel Jungwirth
Jan 24, 2009·Biochemistry·Maite RocaArieh Warshel
Jan 1, 2008·PMC Biophysics·Kemper TalleyEmil Alexov
Sep 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Maria P FrushichevaArieh Warshel
Nov 19, 2013·PeerJ·Martin Peter AnderssonSusan Louise Svane Stipp
Jul 15, 2004·FEBS Letters·Anton Burykin, Arieh Warshel
Sep 5, 2002·Proteins·Carlos Adriel Del Carpio-MuñozToshikazu Yoshikawa
Dec 4, 2003·Journal of Computational Chemistry·Holger Gohlke, David A Case
Dec 7, 2007·Angewandte Chemie·Hiroshi Ishikita, Arieh Warshel
Feb 6, 2013·Journal of Computational Chemistry·Michel MasellaPhilippe Cuniasse
Apr 13, 2012·Journal of Computational Chemistry·Chang G Ji, John Z H Zhang
Jan 3, 2013·Journal of Computational Chemistry·Juan ZengYe Mei
Jan 26, 2012·Proteins·Nidhi SinghArieh Warshel
Dec 23, 2011·Chembiochem : a European Journal of Chemical Biology·Maria P Frushicheva, Arieh Warshel
Sep 4, 2004·Biophysical Journal·Ingemar AndréSara Linse
Aug 19, 2007·Biophysical Journal·Kelly BrockEmil Alexov
May 16, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·M P AnderssonS L S Stipp
Dec 26, 2002·Journal of Molecular Recognition : JMR·A V VeselovskyP Janssen
Jul 9, 1999·Journal of Molecular Recognition : JMR·M SchapiraR Abagyan
Jan 16, 2013·Quarterly Reviews of Biophysics·Shina C L KamerlinArieh Warshel
Apr 14, 2017·Journal of Chemical Information and Modeling·Yuna YanJohn Z H Zhang
May 16, 2000·Protein Engineering·B O Brandsdal, A O Smalås
Jun 4, 2013·Physical Chemistry Chemical Physics : PCCP·Fernanda DuarteShina Caroline Lynn Kamerlin
Apr 8, 2017·The Journal of Chemical Physics·Zhaoxi SunJohn Z H Zhang

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