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Title: Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling

Journal Article · · Journal of Computational Chemistry
DOI:https://doi.org/10.1002/jcc.23982· OSTI ID:1327588
 [1];  [2];  [3];  [2];  [4];  [5]
  1. Florida State Univ., Tallahassee, FL (United States). Dept. of Chemistry & Biochemistry
  2. Florida State Univ., Tallahassee, FL (United States). Inst. of Molecular Biophysics
  3. Institute of Molecular Biophysics, Florida State University, Tallahassee Florida 32306
  4. 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
  5. Florida State Univ., Tallahassee, FL (United States). Dept. of Chemistry & Biochemistry; Florida State Univ., Tallahassee, FL (United States). Inst. of Molecular Biophysics
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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.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
Sponsoring Organization:
USDOE Office of Science (SC); Work for Others (WFO); National Science Foundation (NSF)
Grant/Contract Number:
AC05-00OR22725; MCB1158284
OSTI ID:
1327588
Journal Information:
Journal of Computational Chemistry, Vol. 37, Issue 6; ISSN 0192-8651
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

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Cited By (2)

Pore-Selective SnS Functionalization in Honeycomb-Patterned Films by a Breath Figure Process Accompanied by Chemical Reaction journal September 2018
An In Silico study of TiO2 nanoparticles interaction with twenty standard amino acids in aqueous solution journal November 2016

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
free energy calculation
enhanced sampling
membrane permeation