Link between Membrane Composition and Permeability to Drugs

Journal of Chemical Theory and Computation
Chi Hang TseChristophe Chipot

Abstract

Prediction of membrane permeability to small molecules represents an important aspect of drug discovery. First-principles calculations of this quantity require an accurate description of both the thermodynamics and kinetics that underlie translocation of the permeant across the lipid bilayer. In this contribution, the membrane permeability to three drugs, or drug-like molecules, namely, 9-anthroic acid (ANA), 2',3'-dideoxyadenosine (DDA), and hydrocortisone (HYL), are estimated in a pure 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and in a POPC:cholesterol (2:1) mixture. On the basis of independent 2-5-μs free-energy calculations combined with a time-fractional Smoluchowski determination of the diffusivity, the estimated membrane permeabilities to these chemically diverse permeants fall within an order of magnitude from the experimental values obtained in egg-lecithin bilayers, with the exception of HYL in pure POPC. This exception is particularly interesting because the calculated permeability of the sterol-rich bilayer to HYL, in close agreement with the experimental value, is about 600 times lower than that of the pure POPC bilayer to HYL. In contrast, the permeabilities to ANA and DDA differ by less than a factor of 10 b...Continue Reading

References

Jul 1, 1992·Biophysical Journal·T X XiangB D Anderson
Jan 1, 1986·The Journal of Membrane Biology·A Walter, J Gutknecht
Dec 9, 1985·Biochimica Et Biophysica Acta·P L Yeagle
Jun 1, 1994·The Journal of Membrane Biology·T X Xiang, B D Anderson
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 6, 1999·Journal of Pharmaceutical Sciences·J D IrvineJ R Grove
Nov 6, 2001·Progress in Lipid Research·Henna Ohvo-RekiläJ Peter Slotte
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alessandro Laio, Michele Parrinello
Jul 1, 1958·Proceedings of the Society for Experimental Biology and Medicine·S H MADIN, N B DARBY
Sep 19, 2003·Journal of Computer-aided Molecular Design·John C Dearden
Jul 21, 2004·BMC Biochemistry·D Peter Tieleman
Aug 5, 2004·The Journal of Chemical Physics·Jérôme Hénin, Christophe Chipot
Dec 21, 2004·The Journal of Chemical Physics·Emma FalckIlpo Vattulainen
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Apr 11, 2006·The Journal of Membrane Biology·Norbert KucerkaJohn F Nagle
Jun 27, 2006·Biophysical Chemistry·Artem B MamonovRob D Coalson
May 10, 2007·The Journal of Physical Chemistry. B·Sukit Leekumjorn, Amadeu K Sum
Jan 2, 2008·The Journal of General Physiology·John C MathaiMark L Zeidel
Apr 17, 2008·The Journal of Chemical Physics·Eric DarveAndrew Pohorille
Jun 4, 2008·Physical Review Letters·Jianjun PanJohn F Nagle
Jan 17, 2009·Journal of the American Chemical Society·W F Drew BennettD Peter Tieleman
Feb 10, 2009·Journal of the American Chemical Society·Edward HarderBenoît Roux
Mar 5, 2009·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Elijah FlennerIoan Kosztin
Jun 26, 2009·BMC Neurology·Katya TsaiounUNKNOWN Alzheimer's Drug Discovery Foundation
Aug 14, 2009·Journal of the American Chemical Society·W F Drew BennettD Peter Tieleman
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Oct 7, 2010·The Journal of Physical Chemistry. B·Sunhwan JoWonpil Im
Nov 16, 2011·The Journal of Physical Chemistry. B·Hiroaki Saito, Wataru Shinoda
Mar 1, 2012·Journal of the American Chemical Society·Christian L WennbergJochen S Hub
Nov 14, 2012·Journal of Chemical Information and Modeling·K VanommeslaegheA D MacKerell
Nov 14, 2012·Journal of Chemical Information and Modeling·K Vanommeslaeghe, A D MacKerell
Dec 1, 2012·Nature Reviews. Drug Discovery·Joanne BowesSteven Whitebread
Sep 4, 2013·Journal of Computational Chemistry·Christopher G MayneJames C Gumbart
Nov 14, 2013·Journal of Chemical Theory and Computation·Lei Huang, Benoît Roux
Jan 2, 2014·Pharmacological Reviews·Gregory SliwoskiEdward W Lowe
Aug 12, 2014·The Journal of Chemical Physics·Alfredo E Cardenas, Ron Elber
Sep 24, 2014·The Journal of Physical Chemistry. B·Jeffrey ComerChristophe Chipot
Feb 11, 2014·Journal of Chemical Theory and Computation·Jeffrey ComerChristophe Chipot

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Citations

Oct 9, 2019·Molecular Neurobiology·Pekka A Postila, Tomasz Róg
Sep 4, 2019·Journal of Computational Chemistry·Hong ZhangChristophe Chipot
Aug 6, 2020·The Journal of Chemical Physics·James C PhillipsEmad Tajkhorshid
Feb 15, 2020·Scientific Data·Christian HoffmannTristan Bereau
Jul 28, 2020·Frontiers in Bioengineering and Biotechnology·Tommaso CasaliniGiuseppe Perale
Jun 30, 2019·Database : the Journal of Biological Databases and Curation·Jakub JuračkaKarel Berka
Nov 17, 2020·The Journal of Membrane Biology·Victoria T LimDouglas J Tobias
Mar 7, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tommaso Casalini
May 14, 2021·The Journal of Physical Chemistry. B·Yuqin YangHuan-Xiang Zhou
Aug 4, 2021·The Journal of Chemical Physics·Fikret AydinJessica M J Swanson
Mar 6, 2019·ACS Central Science·Roberto MenichettiTristan Bereau
Aug 4, 2018·The Journal of Physical Chemistry Letters·Haohao FuWensheng Cai
Nov 5, 2019·Accounts of Chemical Research·Haohao FuChristophe Chipot
Mar 4, 2020·Journal of Chemical Theory and Computation·Phu K TangSharon M Loverde
Aug 7, 2019·Journal of the American Chemical Society·Zhi YueJessica M J Swanson
Sep 25, 2018·The Journal of Physical Chemistry. B·Magd BadaouiEdina Rosta
Jul 2, 2019·Journal of Chemical Information and Modeling·Andrei L Lomize, Irina D Pogozheva

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