Stochastic level-set variational implicit-solvent approach to solute-solvent interfacial fluctuations

Journal Article · Sun Aug 07 04:00:00 EDT 2016 · Journal of Chemical Physics

DOI:https://doi.org/10.1063/1.4959971· OSTI ID:22679024

Zhou, Shenggao ^[1]; Sun, Hui; Cheng, Li-Tien ^[2]; Dzubiella, Joachim ^[3]; Li, Bo ^[4]; McCammon, J. Andrew ^[5]

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1. Department of Mathematics and Mathematical Center for Interdiscipline Research, Soochow University, 1 Shizi Street, Jiangsu, Suzhou 215006 (China)
2. Department of Mathematics, University of California, San Diego, La Jolla, California 92093-0112 (United States)
3. Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin, 14109 Berlin, Germany and Institut für Physik, Humboldt-Universität zu Berlin, 12489 Berlin (Germany)
4. Department of Mathematics and Quantitative Biology Graduate Program, University of California, San Diego, La Jolla, California 92093-0112 (United States)
5. Department of Chemistry and Biochemistry, Department of Pharmacology, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093-0365 (United States)

Recent years have seen the initial success of a variational implicit-solvent model (VISM), implemented with a robust level-set method, in capturing efficiently different hydration states and providing quantitatively good estimation of solvation free energies of biomolecules. The level-set minimization of the VISM solvation free-energy functional of all possible solute-solvent interfaces or dielectric boundaries predicts an equilibrium biomolecular conformation that is often close to an initial guess. In this work, we develop a theory in the form of Langevin geometrical flow to incorporate solute-solvent interfacial fluctuations into the VISM. Such fluctuations are crucial to biomolecular conformational changes and binding process. We also develop a stochastic level-set method to numerically implement such a theory. We describe the interfacial fluctuation through the “normal velocity” that is the solute-solvent interfacial force, derive the corresponding stochastic level-set equation in the sense of Stratonovich so that the surface representation is independent of the choice of implicit function, and develop numerical techniques for solving such an equation and processing the numerical data. We apply our computational method to study the dewetting transition in the system of two hydrophobic plates and a hydrophobic cavity of a synthetic host molecule cucurbit[7]uril. Numerical simulations demonstrate that our approach can describe an underlying system jumping out of a local minimum of the free-energy functional and can capture dewetting transitions of hydrophobic systems. In the case of two hydrophobic plates, we find that the wavelength of interfacial fluctuations has a strong influence to the dewetting transition. In addition, we find that the estimated energy barrier of the dewetting transition scales quadratically with the inter-plate distance, agreeing well with existing studies of molecular dynamics simulations. Our work is a first step toward the inclusion of fluctuations into the VISM and understanding the impact of interfacial fluctuations on biomolecular solvation with an implicit-solvent approach.

• OSTI ID: 22679024
• Journal Information: Journal of Chemical Physics, Journal Name: Journal of Chemical Physics Journal Issue: 5 Vol. 145; ISSN JCPSA6; ISSN 0021-9606
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
COMPUTERIZED SIMULATION
CONFORMATIONAL CHANGES
DIELECTRIC MATERIALS
FLUCTUATIONS
FREE ENERGY
MOLECULAR DYNAMICS METHOD
NUMERICAL DATA
SOLUTES
SOLVENTS