@article {422, title = {Charge Delocalization in Proton Channels, I: the Aquaporin Channels and Proton Blockage}, journal = {Biophys J}, volume = {92}, number = {1}, year = {2007}, note = {Chen, Hanning Ilan, Boaz Wu, Yujie Zhu, Fangqiang Schulten, Klaus Voth, Gregory A 2 P41 RR05969/RR/NCRR NIH HHS/United States R01 GM067887/GM/NIGMS NIH HHS/United States R01-GM53148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States Biophysical journal Biophys J. 2007 Jan 1;92(1):46-60. Epub 2006 Oct 20.}, pages = {46-60}, abstract = {

The explicit contribution to the free energy barrier and proton conductance from the delocalized nature of the excess proton is examined in aquaporin channels using an accurate all-atom molecular dynamics computer simulation model. In particular, the channel permeation free energy profiles are calculated and compared for both a delocalized (fully Grotthuss shuttling) proton and a classical (nonshuttling) hydronium ion along two aquaporin channels, Aqp1 and GlpF. To elucidate the effects of the bipolar field thought to arise from two alpha-helical macrodipoles on proton blockage, free energy profiles were also calculated for computational mutants of the two channels where the bipolar field was eliminated by artificially discharging the backbone atoms. Comparison of the free energy profiles between the proton and hydronium cases indicates that the magnitude of the free energy barrier and position of the barrier peak for the fully delocalized and shuttling proton are somewhat different from the case of the (localized) classical hydronium. The proton conductance through the two aquaporin channels is also estimated using Poisson-Nernst-Planck theory for both the Grotthuss shuttling excess proton and the classical hydronium cation.

}, keywords = {Aquaporin 1/*chemistry Aquaporins/*chemistry Biological Transport Biophysics/*methods Escherichia coli Proteins/*chemistry Ions Models, Chemical Models, Molecular Models, Secondary Protons Thermodynamics, Statistical Mutation Oxygen/chemistry Protein Structure}, doi = {10.1529/biophysj.106.091934}, author = {Chen, H. and B. Ilan and Y. Wu and Zhu, F. and K. Schulten and G. A. Voth} } @article {522, title = {Evaluation of Nonlinear Quantum Time Correlation Functions within the Centroid Dynamics Formulation}, journal = {J Phys Chem B}, volume = {110}, number = {38}, year = {2006}, note = {Krishna, Vinod Voth, Gregory A Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The journal of physical chemistry. B J Phys Chem B. 2006 Sep 28;110(38):18953-7.}, pages = {18953-7}, abstract = {

A method to evaluate nonlinear centroid correlation functions is presented that is amenable to simple numerical computation. It can be implemented with the centroid molecular dynamics method for approximate quantum dynamics with no additional assumptions. Two nonlinear correlation functions are evaluated for a model potential using this scheme and compared with results from exact quantum calculations.

}, keywords = {Models, Molecular Models, Theoretical *Quantum Theory}, doi = {10.1021/jp060073q}, author = {Krishna, V. and G. A. Voth} } @article {395, title = {The Properties of Ion-water Clusters. II. Solvation Structures of Na+, Cl-, and H+ Clusters as a Function of Temperature}, journal = {J Chem Phys}, volume = {124}, number = {2}, year = {2006}, note = {Burnham, Christian J Petersen, Matt K Day, Tyler J F Iyengar, Srinivasan S Voth, Gregory A 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):024327.}, pages = {024327}, abstract = {

Ion-water-cluster properties are investigated both through the multistate empirical valence bond potential and a polarizable model. Equilibrium properties of the ion-water clusters H+(H2O)100, Na+(H2O)100, Na+(H2O)20, and Cl-(H2O)17 in the temperature region 100-450 K are explored using a hybrid parallel basin-hopping and tempering algorithm. The effect of the solid-liquid phase transition in both caloric curves and structural distribution functions is investigated. It is found that sodium and chloride ions largely reside on the surface of water clusters below the cluster melting temperature but are solvated into the interior of the cluster above the melting temperature, while the solvated proton was found to have significant propensity to reside on or near the surface in both the liquid- and solid-state clusters.

}, keywords = {Algorithms Calorimetry Chemistry, Molecular Models, Physical/*methods Chlorides/*chemistry Chlorine/chemistry Computer Simulation Ions Models, Statistical Models, Theoretical Monte Carlo Method *Protons Sodium/*chemistry Temperature Water/*chemistry}, doi = {10.1063/1.2149375}, author = {C. J. Burnham and Petersen, M. K. and Day, T. J. and S. S. Iyengar and G. A. Voth} } @article {701, title = {Tail Aggregation and Domain Diffusion in Ionic Liquids}, journal = {J Phys Chem B}, volume = {110}, number = {37}, year = {2006}, note = {Wang, Yanting Voth, Gregory A Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The journal of physical chemistry. B J Phys Chem B. 2006 Sep 21;110(37):18601-8.}, pages = {18601-8}, abstract = {

An extended multiscale coarse-graining model for ionic liquids is used to investigate the liquid crystal-like phase in certain ionic liquids. The tail groups of the cations with a sufficient side-chain length are found to aggregate, forming spatially heterogeneous domains, due to the competition between the electrostatic interactions between the charged head groups and the anions and the collective short-range interactions between the neutral tail groups. With a sufficiently long alkyl chain at a low enough temperature, the tail domains remain relatively stable, despite the diffusion of individual ions in the liquid phase. With increasing temperature, the average tail domains begin to diffuse, while beyond a transition temperature, their average density has an almost uniform distribution, although the tail groups still form instantaneous domains.

}, keywords = {Carbon/chemistry Cations Chemistry, Molecular Models, Physical/*methods Diffusion Gas Chromatography-Mass Spectrometry/methods *Ions Liquid Crystals Models, Statistical Software Solvents Static Electricity Temperature}, doi = {10.1021/jp063199w}, author = {Wang, Y. and G. A. Voth} } @article {713, title = {Computer Simulation of Explicit Proton Translocation in Cytochrome c Oxidase: the D-pathway}, journal = {Proc Natl Acad Sci U S A}, volume = {102}, number = {19}, year = {2005}, note = {Xu, Jiancong Voth, Gregory A R01 GM053148/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2005 May 10;102(19):6795-800. Epub 2005 Apr 27.}, pages = {6795-800}, abstract = {

Proton translocation in the D-pathway of cytochrome c oxidase has been studied by a combination of classical molecular dynamics and the multistate empirical valence bond methodology. This approach allows for explicit Grotthuss proton hopping between water molecules. According to mutagenesis experiments, the role of proton donor/acceptor along the D-pathway is carried by the highly conserved residue Glu-242. The present multistate empirical valence bond simulations indicate that the protonation/deprotonation state of Glu-242 is strongly coupled to the distance of proton propagation in the D-pathway. The proton was seen to travel the full length of the D-pathway when Glu-242 was deprotonated; however, it was trapped halfway along the path when Glu-242 was protonated. Further investigation in terms of both proton dynamical properties and free energy calculations for the pathway of proton transport provides evidence for a two-step proton transport mechanism in the D-pathway.

}, keywords = {Animals Biophysics/*methods Cattle Computer Simulation Crystallography, Molecular Models, Statistical Mutagenesis Protons Serine/chemistry Static Electricity Thermodynamics Time Factors Water/chemistry, X-Ray Electron Transport Complex IV/*chemistry Glutamic Acid/chemistry Mitochondria/metabolism Models}, doi = {10.1073/pnas.0408117102}, author = {Xu, J. and G. A. Voth} } @article {499, title = {The Dynamic Stress Responses to Area Change in Planar Lipid Bilayer Membranes}, journal = {Biophys J}, volume = {88}, number = {2}, year = {2005}, note = {Jeon, Jonggu Voth, Gregory A R01 GM63796/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Biophysical journal Biophys J. 2005 Feb;88(2):1104-19. Epub 2004 Nov 12.}, pages = {1104-19}, abstract = {

The viscoelastic properties of planar phospholipid (dimyristoylphosphatidylcholine) bilayer membranes at 308 K are studied, many of them for the first time, using the nonequilibrium molecular dynamics simulation (NEMD) method for membrane area change. First, we present a unified formulation of the intrinsic three-dimensional (3D) and apparent in-plane viscoelastic moduli associated with area change based on the constitutive relations for a uniaxial system. The NEMD simulations of oscillatory area change process are then used to obtain the frequency-domain moduli. In the 4-250 GHz range, the intrinsic 3D elastic moduli of 20-27 kbar and viscous moduli of 0.2-9 kbar are found with anisotropy and monotonic frequency dispersion. In contrast, the apparent in-plane elastic moduli (1-9 kbar) are much smaller than, and the viscous moduli (2-6 kbar) comparable to, their 3D counterparts, due to the interplay between the lateral and normal relaxations. The time-domain relaxation functions, separately obtained by applying stepwise strains, can be fit by 4-6 exponential decay modes spanning subpicosecond to nanosecond timescale and are consistent with the frequency-domain results. From NEMD with varying strain amplitude, the linear constitutive model is shown to be valid up to 6 and 20\% area change for the intrinsic 3D elastic and viscous responses, respectively, and up to 20\% area change for the apparent in-plane viscoelasticity. Inclusion of a gramicidin A dimer (approximately 1 mol \%) yields similar response properties with possibly smaller (\<10\%) viscous moduli. Our results agree well with available data from ultrasonic experiments, and demonstrate that the third dimension (thickness) of the planar lipid bilayer is integral to the in-plane viscoelasticity.

}, keywords = {Artificial *Models, Chemical *Models, Dimyristoylphosphatidylcholine/*chemistry Elasticity Kinetics Linear Models Lipid Bilayers/*chemistry *Membrane Fluidity Membranes, Mechanical Surface Tension, Molecular Models, Statistical Motion Oscillometry/methods Physical Stimulation/methods Stress}, doi = {10.1529/biophysj.104.052183}, author = {J. Jeon and G. A. Voth} } @article {482, title = {A Multiscale Coarse-Graining Method for Biomolecular Systems}, journal = {J Phys Chem B}, volume = {109}, number = {7}, year = {2005}, note = {Izvekov, Sergei Voth, Gregory A Letter Research Support, U.S. Gov{\textquoteright}t, Non-P.H.S. United States The journal of physical chemistry. B J Phys Chem B. 2005 Feb 24;109(7):2469-73.}, pages = {2469-73}, abstract = {

A new approach is presented for obtaining coarse-grained (CG) force fields from fully atomistic molecular dynamics (MD) trajectories. The method is demonstrated by applying it to derive a CG model for the dimyristoylphosphatidylcholine (DMPC) lipid bilayer. The coarse-graining of the interparticle force field is accomplished by an application of a force-matching procedure to the force data obtained from an explicit atomistic MD simulation of the biomolecular system of interest. Hence, the method is termed a "multiscale" CG (MS-CG) approach in which explicit atomistic-level forces are propagated upward in scale to the coarse-grained level. The CG sites in the lipid bilayer application were associated with the centers-of-mass of atomic groups because of the simplicity in the evaluation of the forces acting on them from the atomistic data. The resulting CG lipid bilayer model is shown to accurately reproduce the structural properties of the phospholipid bilayer.

}, keywords = {Chemical Models, Chemistry, Molecular Models, Physical/*methods Computer Simulation Dimyristoylphosphatidylcholine/*chemistry Lipid Bilayers/*chemistry Models, Statistical Molecular Conformation Phospholipids/*chemistry}, doi = {10.1021/jp044629q}, author = {Izvekov, S. 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} } @article {648, title = {Molecular Dynamics Simulation of Proton Transport Near the Surface of a Phospholipid Membrane}, journal = {Biophys J}, volume = {82}, number = {3}, year = {2002}, note = {Smondyrev, Alexander M Voth, Gregory A GM53148/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Biophysical journal Biophys J. 2002 Mar;82(3):1460-8.}, pages = {1460-8}, abstract = {

The structural and dynamical properties of a hydrated proton near the surface of DMPC membrane were studied using a molecular dynamics simulation. The proton transport between water molecules was modeled using the second generation multistate empirical valence bond model. The proton diffusion was found to be inhibited at the membrane surface. The potential of mean force for the proton adsorption to the membrane surface and its release back into the bulk water was also determined, yielding a small barrier in each direction. An efficient algorithm for Ewald summation calculations for the multistate empirical valence bond model is also introduced.

}, keywords = {Adsorption Algorithms Biological Transport Cell Membrane/*metabolism Diffusion Dimyristoylphosphatidylcholine/chemistry Lipids/chemistry Models, Molecular Models, Statistical Phospholipids/*chemistry *Protons Water/chemistry}, doi = {10.1016/S0006-3495(02)75500-8}, author = {Smondyrev, A. M. and G. A. Voth} } @article {647, title = {Molecular Dynamics Simulation of Proton Transport through the Influenza A Virus M2 Channel}, journal = {Biophys J}, volume = {83}, number = {4}, year = {2002}, note = {Smondyrev, Alexander M Voth, Gregory A GM-53148/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov{\textquoteright}t, P.H.S. United States Biophysical journal Biophys J. 2002 Oct;83(4):1987-96.}, pages = {1987-96}, abstract = {

The structural and dynamical properties of a solvated proton in the influenza A virus M2 channel are studied using a molecular dynamics (MD) simulation technique. The second-generation multi-state empirical valence bond (MS-EVB2) model was used to describe the interaction between the excess proton and the channel environment. Solvation structures of the excess proton and its mobility characteristics along the channel were determined. It was found that the excess proton is capable of crossing the channel gate formed by the ring of four histidine residues even though the gate was only partially open. Although the hydronium ion itself did not cross the channel gate by traditional diffusion, the excess proton was able to transport through the ring of histidine residues by hopping between two water molecules located at the opposite sides of the gate. Our data also indicate that the proton diffusion through the channel may be correlated with the changes in channel conformations. To validate this observation, a separate simulation of the proton in a "frozen" channel has been conducted, which showed that the proton mobility becomes inhibited.

}, keywords = {Biological Transport Biophysical Phenomena Biophysics Carbon/chemistry Computer Simulation Diffusion Dimyristoylphosphatidylcholine/chemistry Influenza A virus/*metabolism Ion Channel Gating Ion Channels/chemistry/physiology Lipid Bilayers/*chemistry Mode, Molecular Models, Statistical Protons Time Factors Viral Matrix Proteins/*chemistry/*physiology}, doi = {10.1016/S0006-3495(02)73960-X}, author = {Smondyrev, A. M. and G. A. Voth} }