title: Comparative exploration of hydrogen sulfide and water transmembrane free energy surfaces via orthogonal space tempering free energy sampling.
abstract: Hydrogen sulfide (H2 S), 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 H2 S and its structural analogue, water (H2 O), seeking to decipher the molecular determinants that govern their drastically different permeabilities. 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 H2 S 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 H2 S 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. This study not only explains why H2 S 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. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Chemistry & Biochemistry, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Erick W
authors.initials: EW
authors.lastname: Aitchison
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Zheng
authors.affiliation: UT-ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37830.|Department of Biochemistry, Cellular and Molecular Biology, the University of Tennessee, Knoxville, Tennessee, 37996.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Chemistry & Biochemistry, Florida State University, Tallahassee, Florida, 32306.|Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D013816:Thermodynamics; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014867:Water; D006862:Hydrogen Sulfide
keywords: enhanced sampling; free energy calculation; membrane permeation