Computational mapping identifies the binding sites of organic solvents on proteins

Proceedings of the National Academy of Sciences of the United States of America
S DennisSandor Vajda

Abstract

Computational mapping places molecular probes--small molecules or functional groups--on a protein surface to identify the most favorable binding positions. Although x-ray crystallography and NMR show that organic solvents bind to a limited number of sites on a protein, current mapping methods result in hundreds of energy minima and do not reveal why some sites bind molecules with different sizes and polarities. We describe a mapping algorithm that explains the origin of this phenomenon. The algorithm has been applied to hen egg-white lysozyme and to thermolysin, interacting with eight and four different ligands, respectively. In both cases the search finds the consensus site to which all molecules bind, whereas other positions that bind only certain ligands are not necessarily found. The consensus sites are pockets of the active site, lined with partially exposed hydrophobic residues and with a number of polar residues toward the edge. These sites can accommodate each ligand in a number of rotational states, some with a hydrogen bond to one of the nearby donor/acceptor groups. Specific substrates and/or inhibitors of hen egg-white lysozyme and thermolysin interact with the same side chains identified by the mapping, but form se...Continue Reading

References

Feb 1, 1992·Journal of Computer-aided Molecular Design·H J Böhm
Jul 7, 1995·Journal of Molecular Biology·R M Jackson, M J Sternberg
Jan 1, 1995·Annual Review of Biophysics and Biomolecular Structure·R RosenfeldC DeLisi
May 26, 1995·Science·B Honig, A Nicholls
Jun 11, 1993·Journal of Medicinal Chemistry·S H Rotstein, M A Murcko
Nov 29, 1996·Science·S B ShukerS W Fesik
Mar 1, 1997·Nature Biotechnology·E Liepinsh, G Otting
May 1, 1996·Nature Biotechnology·C Mattos, D Ringe

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Citations

Jun 13, 2009·Journal of Computer-aided Molecular Design·Melissa R LandonDagmar Ringe
Jun 10, 2009·Journal of Computer-aided Molecular Design·Christian R Schubert, Collin M Stultz
Sep 23, 2003·Journal of Molecular Biology·Michael SilbersteinSandor Vajda
Oct 28, 2009·Biochemistry·Chi-Ho NganSandor Vajda
Jul 10, 2012·Journal of Chemical Information and Modeling·Brandon S ZerbeDima Kozakov
Dec 17, 2010·Journal of the American Chemical Society·Katrina W Lexa, Heather A Carlson
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dima KozakovSandor Vajda
Dec 21, 2004·Nucleic Acids Research·Shu-Hsien SheuSandor Vajda
Oct 4, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Akifumi Oda
Nov 22, 2011·Future Medicinal Chemistry·Jutta WannerJohn Roberts
Jun 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rushikesh Sable, Seetharama Jois
Aug 30, 2011·European Journal of Cell Biology·Robert AdamsRobert Preissner
Jun 28, 2011·Current Opinion in Chemical Biology·Eric B FaumanEnoch S Huang
Jul 21, 2010·Journal of Molecular Biology·Avraham Ben-Shimon, Miriam Eisenstein
Aug 1, 2015·Journal of Medicinal Chemistry·Dima KozakovSandor Vajda
Jul 1, 2010·Protein Science : a Publication of the Protein Society·Gwo-Yu ChuangLesa J Beamer
Feb 21, 2006·Journal of Molecular Biology·Carla MattosDagmar Ringe
Dec 27, 2005·Drug Discovery Today·Philip J HajdukChristin Tse
Apr 1, 2015·Future Medicinal Chemistry·David R Hall, Istvan J Enyedy
Feb 24, 2015·Computational Biology and Chemistry·Aditi Gangopadhyay, Abhijit Datta
Nov 18, 2009·Biophysical Journal·Gwo-Yu ChuangSandor Vajda
May 24, 2005·Biophysical Journal·Dima KozakovCarlos J Camacho
Sep 4, 2013·Journal of Biomolecular Structure & Dynamics·Kalpana Pandey Ashish
Feb 13, 2016·Journal of Medicinal Chemistry·Peter W KennyGeraldo Rodrigues Sartori
Oct 28, 2015·PLoS Computational Biology·Priyanka PrakashAlemayehu A Gorfe
Jul 10, 2016·Drug Discovery Today·Olgun Guvench
Aug 4, 2016·Journal of Medicinal Chemistry·Phani Ghanakota, Heather A Carlson
Sep 16, 2016·Future Medicinal Chemistry·David R Hall, Istvan J Enyedy
Nov 6, 2015·Trends in Pharmacological Sciences·David R HallSandor Vajda
Apr 5, 2017·Journal of Medicinal Chemistry·Prakash Chandra RathiMarcel L Verdonk
Mar 11, 2005·Molecular & Cellular Proteomics : MCP·Jianghong AnRuben Abagyan

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