Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design

Biophysical Journal
Wei ChenM K Gilson

Abstract

The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of alpha-, beta-, and gamma-cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone. These calculations require hours to a day on a commodity computer. The calculations also indicate that the changes in configurational entropy upon binding oppose association by as much as 24 kcal/mol and result primarily from a narrowing of energy wells in the bound versus the free state, rather than from a drop in the number of distinct low-energy conformations on binding. Also, the configurational entropy is found to vary substantially among the bound conformations of a given cyclodextrin-guest complex. This result suggests that the configurational entropy must be accounted for to reliably rank docked conformations in both host-guest and ligand-protein complexes. In close analogy with the common experimental observation of entropy-enthalpy compensation, the computed entropy changes show a near-linear relationship with the changes in mean potential plus solvation energy.

References

Feb 1, 1991·Journal of Computer-aided Molecular Design·M K Gilson, B Honig
Jun 5, 1982·Journal of Molecular Biology·J Warwicker, H C Watson
Oct 1, 1995·Biophysical Journal·R A Friedman, B Honig
Feb 1, 1997·Chemistry & Biology·M K GilsonM S Head
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Mar 29, 2001·Journal of Computer-aided Molecular Design·L DavidM K Gilson
May 10, 2001·Protein Science : a Publication of the Protein Society·K Sharp
May 24, 2001·Journal of Molecular Biology·K L MardisM K Gilson
Feb 19, 2002·Chemical Reviews·Mikhail V. Rekharsky, Yoshihisa Inoue
Oct 24, 2002·Journal of Computational Chemistry·Visvaldas Kairys, Michael K Gilson
Apr 7, 2004·Journal of Pharmaceutical Sciences·Thorsteinn LoftssonMarcus E Brewster
Apr 20, 2004·Current Opinion in Structural Biology·Michael Feig, Charles L Brooks
Jul 27, 2004·Journal of Chemical Information and Computer Sciences·Wei ChenMichael K Gilson
Oct 8, 2004·Journal of the American Chemical Society·Chia-En Chang, Michael K Gilson
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus

❮ Previous
Next ❯

Citations

Apr 14, 2010·Journal of Molecular Modeling·Claudio Carra, Francis A Cucinotta
Oct 12, 2010·Journal of Computer-aided Molecular Design·Constanza CárdenasF Javier Luque
Dec 27, 2011·Journal of Computer-aided Molecular Design·Traian SuleaEnrico O Purisima
Jan 26, 2012·Journal of Computer-aided Molecular Design·Hari S Muddana, Michael K Gilson
Mar 1, 2012·Journal of Computer-aided Molecular Design·Hari S MuddanaMichael K Gilson
Apr 17, 2013·Journal of Chromatography. a·Darren DeSoiH Thomas Karnes
Apr 20, 2005·Current Opinion in Structural Biology·Tomas Rodinger, Régis Pomès
Nov 16, 2011·Quarterly Reviews of Biophysics·Jeff Wereszczynski, J Andrew McCammon
Jul 1, 2011·Journal of Chemical Information and Modeling·Traian SuleaEnrico O Purisima
Apr 14, 2012·Journal of Chemical Information and Modeling·Junmei Wang, Tingjun Hou
Jul 11, 2009·Chemical Reviews·Huan-Xiang Zhou, Michael K Gilson
Jan 13, 2009·Journal of the American Chemical Society·Sarvin MoghaddamMichael K Gilson
Sep 13, 2008·Journal of Medicinal Chemistry·Pietro CozziniChristoph A Sotriffer
May 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ian F Thorpe, Charles L Brooks
Jan 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Chia-en A ChangMichael K Gilson
Jan 5, 2007·Annual Review of Biophysics and Biomolecular Structure·Michael K Gilson, Huan-Xiang Zhou
Nov 16, 2013·PloS One·Karunakar Tanneeru, Lalitha Guruprasad
Dec 2, 2011·The Journal of Chemical Physics·Olivia Wise-SciraOrkid Coskuner
May 2, 2009·The Journal of Chemical Physics·F Marty Ytreberg
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mikhail V RekharskyYoshihisa Inoue
Mar 7, 2014·Journal of Computer-aided Molecular Design·Hari S MuddanaMichael K Gilson
Feb 11, 2014·Journal of Computer-aided Molecular Design·Hari S MuddanaMichael K Gilson
Jan 30, 2014·Journal of Computer-aided Molecular Design·Hervé HoguesEnrico O Purisima
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Leonid M Berezhkovskiy
Jul 29, 2010·Journal of Pharmaceutical Sciences·Kenjirou HigashiKeiji Yamamoto
Aug 11, 2015·Journal of Molecular Recognition : JMR·Lauren WickstromRonald M Levy
Jun 21, 2011·Current Opinion in Chemical Biology·Anita de Ruiter, Chris Oostenbrink
Sep 26, 2015·Journal of Molecular Graphics & Modelling·Summer KassemKhaled H Barakat
Aug 12, 2008·Journal of Molecular Biology·Agustina Rodriguez-GranilloPernilla Wittung-Stafshede
Nov 15, 2005·Biophysical Journal·Michael S Lee, Mark A Olson
May 21, 2009·Biotechnology Progress·Jacob M VasquezValentine I Vullev
Mar 2, 2011·Journal of Molecular Recognition : JMR·Alina AsandeiTudor Luchian
Aug 25, 2015·Journal of Chemical Information and Modeling·Wasinee KhuntaweeSupot Hannongbua
Aug 19, 2015·Journal of Chemical Information and Modeling·Hervé HoguesEnrico O Purisima
Apr 15, 2016·Chemical Reviews·Ulf Ryde, Pär Söderhjelm
Sep 24, 2014·Journal of Biomolecular Structure & Dynamics·Karunakar TanneeruLalitha Guruprasad

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Chia-En A ChangM K Gilson
Journal of Chemical Theory and Computation
Wei ChenMichael J Potter
Annual Review of Biophysics and Biomolecular Structure
M K Gilson, Huan-Xiang Zhou
Journal of Computational Chemistry
Chia-En Chang, M K Gilson
© 2021 Meta ULC. All rights reserved