PMID: 9542997May 23, 1998Paper

A fast estimate of electrostatic group contributions to the free energy of protein-inhibitor binding

Protein Engineering
I MueggeArieh Warshel

Abstract

Dissecting ligand-protein binding free energies in individual contributions of protein residues (which are referred to here as 'group contributions') is of significant importance. For example, such contributions could help in estimating the corresponding mutational effects and in studies of drug resistance problems. However, the meaning of group contributions is not always uniquely defined and the approximations for rapid estimates of such contributions are not well developed. In this paper, the nature of group contributions to binding free energy is examined, focusing particularly on electrostatic contributions which are expected to be well behaved. This analysis examines different definitions of group contributions; the 'relaxed' group contributions that represent the change in binding energy upon mutation of the given residue to glycine, and the 'non-relaxed' group contributions that represent the scaled Coulomb interaction between the given residue and the ligand. Both contributions are defined and evaluated by the linear response approximation (LRA) of the PDLD/ S method. The present analysis considers the binding of pepstatin to endothiapepsin and 23 of its mutants as a test case for a neutral ligand. The 'non-relaxed' gr...Continue Reading

Citations

Oct 10, 2006·Biophysical Chemistry·M A Olson
Jun 19, 1998·Current Opinion in Structural Biology·A Warshel, A Papazyan
Jan 24, 2009·Biochemistry·Maite RocaArieh Warshel
Jun 4, 2013·Physical Chemistry Chemical Physics : PCCP·Fernanda DuarteShina Caroline Lynn Kamerlin
Apr 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hanbin LiuArieh Warshel
May 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Andrew J Adamczyk, Arieh Warshel
Sep 26, 2009·PLoS Computational Biology·Yemin ShiXiaojiang S Chen
Nov 3, 2010·Annual Review of Physical Chemistry·Shina C L KamerlinArieh Warshel
Jun 21, 2015·Journal of the American Chemical Society·Alexandre BarrozoShina C L Kamerlin
Nov 4, 2015·ACS Catalysis·Beat A AmreinShina C L Kamerlin
Jan 26, 2012·Proteins·Nidhi SinghArieh Warshel
Apr 29, 2014·Current Opinion in Chemical Biology·Monika Fuxreiter, Letif Mones
May 17, 2005·Biophysical Journal·Ran FriedmanMenachem Gutman
Apr 12, 2014·The Journal of Physical Chemistry. B·Alexey AleksandrovMartin Field
May 31, 2017·Physical Chemistry Chemical Physics : PCCP·Zhao X SunJohn Z H Zhang
Jul 8, 2017·Journal of the American Chemical Society·Yashraj S KulkarniShina C L Kamerlin
Mar 7, 2018·Organic & Biomolecular Chemistry·Alexandre BarrozoShina Caroline Lynn Kamerlin
Jul 15, 2004·FEBS Letters·Anton Burykin, Arieh Warshel
Dec 23, 2011·Chembiochem : a European Journal of Chemical Biology·Maria P Frushicheva, Arieh Warshel
Sep 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Chen Bai, Arieh Warshel
Aug 25, 2020·Chemical Science·Valeria A RissoShina C L Kamerlin
Mar 27, 2015·Chemistry : a European Journal·Avital Sharir-IvryAvital Shurki
Jul 20, 1999·Journal of Medicinal Chemistry·I MueggeS W Fesik
Jul 14, 2021·Journal of the American Chemical Society·Chen BaiArieh Warshel
Jun 24, 2017·Journal of Chemical Information and Modeling·Zhaoxi SunJianing Song
Jun 15, 2019·Journal of the American Chemical Society·Ana R CalixtoShina C L Kamerlin
Nov 13, 2020·Journal of the American Chemical Society·Michal BilerShina Caroline Lynn Kamerlin

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