Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling
Abstract
Hydrogen sulfide (H2S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H2S and its structural analogue, water (H2O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. Here, as revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is, the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H2S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. Lastly, this study not only explains why H2S can quickly pass through cell membranesmore »
- Authors:
-
- Florida State Univ., Tallahassee, FL (United States). Dept. of Chemistry & Biochemistry
- Florida State Univ., Tallahassee, FL (United States). Inst. of Molecular Biophysics
- Institute of Molecular Biophysics, Florida State University, Tallahassee Florida 32306
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). UT-ORNL Center for Molecular Biophysics; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry, Cellular and Molecular Biology
- Florida State Univ., Tallahassee, FL (United States). Dept. of Chemistry & Biochemistry; Florida State Univ., Tallahassee, FL (United States). Inst. of Molecular Biophysics
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
- Sponsoring Org.:
- USDOE Office of Science (SC); Work for Others (WFO); National Science Foundation (NSF)
- OSTI Identifier:
- 1327588
- Grant/Contract Number:
- AC05-00OR22725; MCB1158284
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Computational Chemistry
- Additional Journal Information:
- Journal Volume: 37; Journal Issue: 6; Journal ID: ISSN 0192-8651
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; free energy calculation; enhanced sampling; membrane permeation
Citation Formats
Lv, Chao, Aitchison, Erick W., Wu, Dongsheng, Zheng, Lianqing, Cheng, Xiaolin, and Yang, Wei. Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling. United States: N. p., 2015.
Web. doi:10.1002/jcc.23982.
Lv, Chao, Aitchison, Erick W., Wu, Dongsheng, Zheng, Lianqing, Cheng, Xiaolin, & Yang, Wei. Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling. United States. https://doi.org/10.1002/jcc.23982
Lv, Chao, Aitchison, Erick W., Wu, Dongsheng, Zheng, Lianqing, Cheng, Xiaolin, and Yang, Wei. Mon .
"Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling". United States. https://doi.org/10.1002/jcc.23982. https://www.osti.gov/servlets/purl/1327588.
@article{osti_1327588,
title = {Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling},
author = {Lv, Chao and Aitchison, Erick W. and Wu, Dongsheng and Zheng, Lianqing and Cheng, Xiaolin and Yang, Wei},
abstractNote = {Hydrogen sulfide (H2S), a commonly known toxic gas compound, possesses unique chemical features that allow this small solute molecule to quickly diffuse through cell membranes. Taking advantage of the recent orthogonal space tempering (OST) method, we comparatively mapped the transmembrane free energy landscapes of H2S and its structural analogue, water (H2O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. Here, as revealed by our OST sampling results, in contrast to the highly polar water solute, hydrogen sulfide is evidently amphipathic, and thus inside membrane is favorably localized at the interfacial region, that is, the interface between the polar head-group and nonpolar acyl chain regions. Because the membrane binding affinity of H2S is mainly governed by its small hydrophobic moiety and the barrier height inbetween the interfacial region and the membrane center is largely determined by its moderate polarity, the transmembrane free energy barriers to encounter by this toxic molecule are very small. Moreover when H2S diffuses from the bulk solution to the membrane center, the above two effects nearly cancel each other, so as to lead to a negligible free energy difference. Lastly, this study not only explains why H2S can quickly pass through cell membranes but also provides a practical illustration on how to use the OST free energy sampling method to conveniently analyze complex molecular processes.},
doi = {10.1002/jcc.23982},
journal = {Journal of Computational Chemistry},
number = 6,
volume = 37,
place = {United States},
year = {Mon Jun 29 00:00:00 EDT 2015},
month = {Mon Jun 29 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function
journal, September 2007
- Elrod, J. W.; Calvert, J. W.; Morrison, J.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 39
A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide
journal, November 2007
- Lefer, D. J.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 46
Putative biological roles of hydrogen sulfide in health and disease: a breath of not so fresh air?
journal, February 2008
- Li, L.; Moore, P.
- Trends in Pharmacological Sciences, Vol. 29, Issue 2
Water and nonelectrolyte permeability of lipid bilayer membranes
journal, August 1976
- Finkelstein, A.
- The Journal of General Physiology, Vol. 68, Issue 2
No facilitator required for membrane transport of hydrogen sulfide
journal, September 2009
- Mathai, J. C.; Missner, A.; Kugler, P.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 39
Permeation Process of Small Molecules across Lipid Membranes Studied by Molecular Dynamics Simulations
journal, January 1996
- Marrink, Siewert J.; Berendsen, Herman J. C.
- The Journal of Physical Chemistry, Vol. 100, Issue 41
Permeation of Small Molecules through a Lipid Bilayer: A Computer Simulation Study
journal, April 2004
- Bemporad, Daniele; Essex, Jonathan W.; Luttmann, Claude
- The Journal of Physical Chemistry B, Vol. 108, Issue 15
Behaviour of small solutes and large drugs in a lipid bilayer from computer simulations
journal, December 2005
- Bemporad, D.; Luttmann, C.; Essex, J. W.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1718, Issue 1-2
Potential of Mean Force and p K a Profile Calculation for a Lipid Membrane-Exposed Arginine Side Chain
journal, August 2008
- Li, Libo; Vorobyov, Igor; Allen, Toby W.
- The Journal of Physical Chemistry B, Vol. 112, Issue 32
Distribution of Amino Acids in a Lipid Bilayer from Computer Simulations
journal, May 2008
- MacCallum, Justin L.; Bennett, W. F. Drew; Tieleman, D. Peter
- Biophysical Journal, Vol. 94, Issue 9
Statistical Convergence of Equilibrium Properties in Simulations of Molecular Solutes Embedded in Lipid Bilayers
journal, October 2011
- Neale, Chris; Bennett, W. F. Drew; Tieleman, D. Peter
- Journal of Chemical Theory and Computation, Vol. 7, Issue 12
Calculation of Lipid-Bilayer Permeabilities Using an Average Force
journal, January 2014
- Comer, Jeffrey; Schulten, Klaus; Chipot, Christophe
- Journal of Chemical Theory and Computation, Vol. 10, Issue 2
Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling
journal, February 1977
- Torrie, G. M.; Valleau, J. P.
- Journal of Computational Physics, Vol. 23, Issue 2
Statistical Mechanics of Fluid Mixtures
journal, May 1935
- Kirkwood, John G.
- The Journal of Chemical Physics, Vol. 3, Issue 5
Constrained reaction coordinate dynamics for the simulation of rare events
journal, April 1989
- Carter, E. A.; Ciccotti, Giovanni; Hynes, James T.
- Chemical Physics Letters, Vol. 156, Issue 5
Random walk in orthogonal space to achieve efficient free-energy simulation of complex systems
journal, December 2008
- Zheng, L.; Chen, M.; Yang, W.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 51
Simultaneous escaping of explicit and hidden free energy barriers: Application of the orthogonal space random walk strategy in generalized ensemble based conformational sampling
journal, June 2009
- Zheng, Lianqing; Chen, Mengen; Yang, Wei
- The Journal of Chemical Physics, Vol. 130, Issue 23
Practically Efficient and Robust Free Energy Calculations: Double-Integration Orthogonal Space Tempering
journal, February 2012
- Zheng, Lianqing; Yang, Wei
- Journal of Chemical Theory and Computation, Vol. 8, Issue 3
λ‐dynamics: A new approach to free energy calculations
journal, August 1996
- Kong, Xianjun; Brooks, Charles L.
- The Journal of Chemical Physics, Vol. 105, Issue 6
Enhancing QM/MM Molecular Dynamics Sampling in Explicit Environments via an Orthogonal-Space-Random-Walk-Based Strategy
journal, April 2011
- Min, Donghong; Chen, Mengen; Zheng, Lianqing
- The Journal of Physical Chemistry B, Vol. 115, Issue 14
Hidden Conformation Events in DNA Base Extrusions: A Generalized-Ensemble Path Optimization and Equilibrium Simulation Study
journal, July 2013
- Cao, Liaoran; Lv, Chao; Yang, Wei
- Journal of Chemical Theory and Computation, Vol. 9, Issue 8
CHARMM-GUI: A web-based graphical user interface for CHARMM
journal, March 2008
- Jo, Sunhwan; Kim, Taehoon; Iyer, Vidyashankara G.
- Journal of Computational Chemistry, Vol. 29, Issue 11
Molecular dynamics simulation of unsaturated lipid bilayers at low hydration: parameterization and comparison with diffraction studies
journal, November 1997
- Feller, S. E.; Yin, D.; Pastor, R. W.
- Biophysical Journal, Vol. 73, Issue 5
Comparison of simple potential functions for simulating liquid water
journal, July 1983
- Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
- The Journal of Chemical Physics, Vol. 79, Issue 2
Constant pressure molecular dynamics simulation: The Langevin piston method
journal, September 1995
- Feller, Scott E.; Zhang, Yuhong; Pastor, Richard W.
- The Journal of Chemical Physics, Vol. 103, Issue 11
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993
- Darden, Tom; York, Darrin; Pedersen, Lee
- The Journal of Chemical Physics, Vol. 98, Issue 12
CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
journal, July 1983
- Brooks, Bernard R.; Bruccoleri, Robert E.; Olafson, Barry D.
- Journal of Computational Chemistry, Vol. 4, Issue 2
CHARMM: The biomolecular simulation program
journal, July 2009
- Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.
- Journal of Computational Chemistry, Vol. 30, Issue 10
Permeability of small nonelectrolytes through lipid bilayer membranes
journal, October 1986
- Walter, Anne; Gutknecht, John
- The Journal of Membrane Biology, Vol. 90, Issue 3
Works referencing / citing this record:
Pore-Selective SnS Functionalization in Honeycomb-Patterned Films by a Breath Figure Process Accompanied by Chemical Reaction
journal, September 2018
- Cao, Thuy Thi; Modigunta, Jeevan Kumar Reddy; Male, Umashankar
- Advanced Materials Interfaces, Vol. 5, Issue 20
An In Silico study of TiO2 nanoparticles interaction with twenty standard amino acids in aqueous solution
journal, November 2016
- Liu, Shengtang; Meng, Xuan-Yu; Perez-Aguilar, Jose Manuel
- Scientific Reports, Vol. 6, Issue 1