@article {618, title = {Effect of Membrane Environment on Proton Permeation through Gramicidin A Channels}, journal = {J. Phys. Chem. B}, volume = {111}, year = {2007}, pages = {9931-9939}, doi = {10.1021/jp0708998}, author = {Qin, Z. and H. L. Tepper and G. A. Voth} } @article {706, title = {Flexible Simple Point-charge Water Model with Improved Liquid-State Properties}, journal = {J Chem Phys}, volume = {124}, number = {2}, year = {2006}, note = {Wu, Yujie Tepper, Harald L Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The Journal of chemical physics J Chem Phys. 2006 Jan 14;124(2):024503.}, pages = {024503}, abstract = {

In order to introduce flexibility into the simple point-charge (SPC) water model, the impact of the intramolecular degrees of freedom on liquid properties was systematically studied in this work as a function of many possible parameter sets. It was found that the diffusion constant is extremely sensitive to the equilibrium bond length and that this effect is mainly due to the strength of intermolecular hydrogen bonds. The static dielectric constant was found to be very sensitive to the equilibrium bond angle via the distribution of intermolecular angles in the liquid: A larger bond angle will increase the angle formed by two molecular dipoles, which is particularly significant for the first solvation shell. This result is in agreement with the work of Hochtl et al. [J. Chem. Phys. 109, 4927 (1998)]. A new flexible simple point-charge water model was derived by optimizing bulk diffusion and dielectric constants to the experimental values via the equilibrium bond length and angle. Due to the large sensitivities, the parametrization only slightly perturbs the molecular geometry of the base SPC model. Extensive comparisons of thermodynamic, structural, and kinetic properties indicate that the new model is much improved over the standard SPC model and its overall performance is comparable to or even better than the extended SPC model.

}, keywords = {Algorithms Chemistry, Physical/*methods Computer Simulation Diffusion Electrochemistry/methods Hydrogen/chemistry Hydrogen Bonding Kinetics Models, Statistical Models, Theoretical Molecular Conformation Oxygen/chemistry Thermodynamics Viscosity Water/*chemistry}, doi = {10.1063/1.2136877}, author = {Y. Wu and H. L. Tepper and G. A. Voth} } @article {662, title = {Mechanisms of Passive Ion Permeation through Lipid Bilayers: Insights from Simulations}, journal = {J Phys Chem B}, volume = {110}, number = {42}, year = {2006}, note = {Tepper, Harald L Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States R01 GM053148/GM/NIGMS NIH HHS/United States R01 GM053148-05/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The journal of physical chemistry. B J Phys Chem B. 2006 Oct 26;110(42):21327-37.}, pages = {21327-37}, abstract = {

Multistate empirical valence bond and classical molecular dynamics simulations were used to explore mechanisms for passive ion leakage through a dimyristoyl phosphatidylcholine lipid bilayer. In accordance with a previous study on proton leakage (Biophys. J. 2005, 88, 3095), it was found that the permeation mechanism must be a highly concerted one, in which ion, solvent, and membrane coordinates are coupled. The presence of the ion itself significantly alters the response of those coordinates, suggesting that simulations of transmembrane water structures without explicit inclusion of the ionic solute are insufficient for elucidating transition mechanisms. The properties of H(+), Na(+), OH(-), and bare water molecules in the membrane interior were compared, both by biased sampling techniques and by constructing complete and unbiased transition paths. It was found that the anomalous difference in leakage rates between protons and other cations can be largely explained by charge delocalization effects rather than the usual kinetic picture (Grotthuss hopping of the proton). Permeability differences between anions and cations through phosphatidylcholine bilayers are correlated with suppression of favorable membrane breathing modes by cations.

}, keywords = {Computer Simulation Dimyristoylphosphatidylcholine Ions/*pharmacokinetics Kinetics Lipid Bilayers/*metabolism Permeability Solvents}, doi = {10.1021/jp064192h}, author = {H. L. Tepper and G. A. Voth} } @article {660, title = {A Coarse-grained Model for Double-helix Molecules in Solution: Spontaneous Helix Formation and Equilibrium Properties}, journal = {J Chem Phys}, volume = {122}, number = {12}, year = {2005}, note = {Tepper, Harald L Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The Journal of chemical physics J Chem Phys. 2005 Mar 22;122(12):124906.}, pages = {124906}, abstract = {

A new reductionist coarse-grained model is presented for double-helix molecules in solution. As with such models for lipid bilayers and micelles, the level of description is both particulate and mesoscopic. The particulate (bead-and-spring) nature of the model makes for a simple implementation in standard molecular dynamics simulation codes and allows for investigation of thermomechanic properties without preimposing any (form of) response function. The mesoscopic level of description{\textendash}where groups of atoms are condensed into coarse-grained beads{\textendash}causes long-range interactions to be effectively screened, which greatly enhances the efficiency and scalability of simulations. Without imposing local or global order parameters, a linear initial configuration of the model molecule spontaneously assembles into a double helix due to the interplay between three contributions: hydrophobic/hydrophilic interactions between base pairs, backbone, and solvent; phosphate-phosphate repulsion along the backbone; and favorable base-pair stacking energy. We present results for the process of helix formation as well as for the equilibrium properties of the final state, and investigate how both depend on the input parameters. The current model holds promise for two routes of investigation: First, within a limited set of generic parameters, the effect of local (atomic-scale) perturbations on overall helical properties can be systematically studied. Second, since the efficiency allows for a direct simulation of both small and large (\>100 base pairs) systems, the model presents a testground for systematic coarse-graining methods.

}, keywords = {Base Pairing Computer Simulation DNA/*chemistry Hydrophobic and Hydrophilic Interactions *Models, Molecular Nucleic Acid Conformation Solutions Solvents/chemistry}, doi = {10.1063/1.1869417}, author = {H. L. Tepper and G. A. Voth} } @article {661, title = {Protons May Leak through Pure Lipid Bilayers via a Concerted Mechanism}, journal = {Biophys J}, volume = {88}, number = {5}, year = {2005}, note = {Tepper, Harald L Voth, Gregory A 1 S10 RR17214-01/RR/NCRR NIH HHS/United States R01 GM053148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Biophysical journal Biophys J. 2005 May;88(5):3095-108. Epub 2005 Feb 4.}, pages = {3095-108}, abstract = {

Protons are known to permeate pure lipid bilayers at a rate that is anomalous compared to those of other small monovalent cations. The prevailing mechanism via which they cross the membrane is still unclear, and it is unknown how to probe the mechanism directly by experiment. One of the more popular theories assumes the formation of membrane-spanning single-file water wires providing a matrix along which the protons can "hop" over the barrier. However, free energy calculations on such structures (without the presence of an excess proton) suggest that this mechanism alone cannot account for the observed permeation rates. We use the multistate empirical valence bond method to directly study water structures surrounding a (delocalized) excess proton on its way through the membrane. We find that membrane-spanning networks, rather than single-file chains, are formed around the proton. We also find that such structures are considerably stabilized in the presence of the proton, with lifetimes of several hundreds of picoseconds. The observed structures are suggestive of a new, concerted, mechanism and provide some direction for further investigation.

}, keywords = {Biophysics/*methods Hydrogen Bonding Ion Channels Lipid Bilayers/*chemistry Membrane Lipids/chemistry Models, Molecular Models, Statistical Oxygen/chemistry Phospholipids/chemistry *Protons Thermodynamics Time Factors Water/chemistry}, doi = {10.1529/biophysj.104.056184}, author = {H. L. Tepper and G. A. Voth} } @article {374, title = {A New Perspective on the Coarse-grained Dynamics of Fluids}, journal = {J Chem Phys}, volume = {120}, number = {9}, year = {2004}, note = {Ayton, Gary S Tepper, Harald L Mirijanian, Dina T Voth, Gregory A R01 GM63796/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States The Journal of chemical physics J Chem Phys. 2004 Mar 1;120(9):4074-88.}, pages = {4074-88}, abstract = {

A computational methodology is presented that is designed to model, at a coarse-grained level, the mesoscale dynamics of fluids and potentially other forms of soft matter. Within a molecular dynamics simulation, "ghost" particles of a specific size, corresponding to the fundamental length-scale of coarse-graining, are used as micro-probes designed to respond to local mesoscale fluid flows and stress gradients. A subsequent coarse-grained model is then developed that incorporates both the coarse-grained mesoscale dynamics and isothermal compressibility of the original microscopic system. The method is applied to water and methanol. A contrast with dissipative particle dynamics (DPD) is also presented.

}, keywords = {Chemical *Models, Colloids/*chemistry Computer Simulation Microfluidics/*methods *Models, Mechanical, Molecular Models, Statistical Molecular Conformation Motion Nanostructures/*chemistry Phase Transition Stress}, doi = {10.1063/1.1644092}, author = {Ayton, G. S. and H. L. Tepper and D. T. Mirijanian and G. A. Voth} }