Particle Mesh Ewald Technique Research Articles

Computing osmotic permeabilities of aquaporins AQP4, AQP5, and GlpF from near-equilibrium simulations

Measuring or computing the single-channel permeability of aquaporins/aquaglyceroporins (AQPs) has long been a challenge. The measured values scatter over an order of magnitude but the corresponding Arrhenius activation energies converge in the current literature. Osmotic flux through an AQP was simulated as water current forced through the channel by kilobar hydraulic pressure or theoretically approximated as single-file diffusion. In this paper, we report large scale simulations of osmotic current under sub M gradient through three AQPs (water channels AQP4 and AQP5 and glycerol-water channel GlpF) using the mature particle mesh Ewald technique (PME) for which the established force fields have been optimized with known accuracy. These simulations were implemented with hybrid periodic boundary conditions devised to avoid the artifactitious mixing across the membrane in a regular PME simulation. The computed single-channel permeabilities at 5°C and 25°C are in agreement with recently refined experiments on GlpF. The Arrhenius activation energies extracted from our simulations for all the three AQPs agree with the in vitro measurements. The single-file diffusion approximations from our large-scale simulations are consistent with the current literature on smaller systems. From these unambiguous agreements among the in vitro and in silico studies, we observe the quantitative accuracy of the all-atom force fields of the current literature for water-channel biology. We also observe that AQP4, that is particularly rich in the central nervous system, is more efficient in water conduction and more temperature-sensitive than other water-only channels (excluding glycerol channels that also conduct water when not inhibited by glycerol).

Scalable evaluation of polarization energy and associated forces in polarizable molecular dynamics: II. Toward massively parallel computations using smooth particle mesh Ewald.

In this article, we present a parallel implementation of point dipole-based polarizable force fields for molecular dynamics (MD) simulations with periodic boundary conditions (PBC). The smooth particle mesh Ewald technique is combined with two optimal iterative strategies, namely, a preconditioned conjugate gradient solver and a Jacobi solver in conjunction with the direct inversion in the iterative subspace for convergence acceleration, to solve the polarization equations. We show that both solvers exhibit very good parallel performances and overall very competitive timings in an energy and force computation needed to perform a MD step. Various tests on large systems are provided in the context of the polarizable AMOEBA force field as implemented in the newly developed Tinker-HP package, which is the first implementation of a polarizable model that makes large-scale experiments for massively parallel PBC point dipole models possible. We show that using a large number of cores offers a significant acceleration of the overall process involving the iterative methods within the context of SPME and a noticeable improvement of the memory management, giving access to very large systems (hundreds of thousands of atoms) as the algorithm naturally distributes the data on different cores. Coupled with advanced MD techniques, gains ranging from 2 to 3 orders of magnitude in time are now possible compared to nonoptimized, sequential implementations, giving new directions for polarizable molecular dynamics with periodic boundary conditions using massively parallel implementations.

How to apply the Kirkwood–Buff theory to individual species in salt solutions

It is generally assumed that the Kirkwood–Buff (KB) theory cannot be applied to anions and cations individually in a solution, as one cannot simulate this system in an open ensemble due to the electroneutrality constraint. By applying our recently derived KB theory for closed systems, we show that one does have access to single-ion properties in Molecular Dynamics. Our findings are supported by simulations for a model of a salt solution in which particles interact with WCA potentials, as well as for the NaCl/water system using the Particle Mesh Ewald technique for electrostatics.

Effect of computational methodology on the conformational dynamics of the protein photosensor LOV1 from Chlamydomonas reinhardtii

LOV domains are the light-sensitive protein domains of plant phototropins and bacteria. They photochemically form a covalent bond between a flavin mononucleotide (FMN) chromophore and a cysteine, attached to the apo-protein, upon irradiation with blue light, which triggers a signal in the adjacent kinase. Although their signaling state has been well characterized through experimental means, their signal transduction pathway as well as dark-state activity are generally only poorly understood. Here we show results from molecular dynamics simulations where we investigated the effect of thermostating and long-range electrostatics on the solution structure and dynamical behavior of the wild-type LOV1 domain from the green algae Chlamydomonas reinhardtii in the dark. We demonstrate that these computational issues can dramatically affect the conformational fluctuations of such protein domains by suppressing configurations far from equilibrium or destabilizing local configurations, leading to artificial changes of the protein secondary structure as well as the H-bond network formed by the amino acids and the FMN. By comparing our calculation results with recent experimental data, we show that the non-invasive thermostating strategy, where the protein solute is only indirectly coupled to the thermostat via the solvent, in conjunction with the particle-mesh Ewald technique, provides dark-state conformers, which are in consistency with experimental observations. Moreover, our calculations indicate that the LOV1 domains can alter the intersystem crossing rate and rate of adduct formation by adjusting the population distribution of these dark-state conformers. This might permit them to function as a modulator of the signal intensity under low light conditions. The online version of this article (doi:10.1007/s12154-011-0060-z) contains supplementary material, which is available to authorized users.

Molecular dynamics study of structural properties of [formula omitted]-sheet assemblies formed by synthetic de novo oligopeptides

We study, by means of molecular dynamics (MD) simulations with explicit water, the structure and stability of β -sheet tapes, ribbons and double ribbons formed by rationally designed oligopeptides P 11 -I and P 11 -II in aqueous solutions. Two different methods for the treatment of the electrostatic interactions were considered: a smoothly shifted spherical cutoff approach under spherical harmonic conditions, and the particle mesh Ewald technique. We investigate the transfer of chirality from single l-aminoacids to the molecular scale of oligopeptides and from the latter to the supramolecular scale of peptide clusters. Furthermore, we obtain structural data for the representative conformations of these clusters, as well as study various average properties of their geometry.

A Molecular Dynamics Study of Tryptophan in Water

Molecular dynamics simulations of a single tryptophan amino acid in water were performed with the CHARMM molecular mechanics program using the modified TIP3P, the refined SPC, and the original SPC/E water models. All these empirical water models are similar in nature, but small differences give significant differences in their properties for liquid water. Nanosecond molecular dynamics simulations were carried out in the NVT, NVE, or NPT ensembles using a cubic simulation cell furnished with periodic boundary conditions. The calculations of long-range interactions were performed with two different methods, the atom-based spherical cutoff method with force shifting, where the nonbonded interactions were smoothly shifted to zero at the cutoff distance, and the particle-mesh Ewald technique. Transition dipole autocorrelation functions and reorientation times of tryptophan were calculated and compared to experimental values. Tryptophan hydration was affected by the water model and the treatment of long-range electrostatic interactions. The reorientation time of tryptophan depended strongly on the water model used, and the viscosity of the model liquid was found to correlate with the tryptophan translational and rotational dynamics in water. Statistical accuracy and errors in the analyses are discussed.

A Nanosecond Molecular Dynamics Study of Antiparallel d(G)7 Quadruplex Structures: Effect of the Coordinated Cations

Nanosecond scale molecular dynamics simulations have been performed on antiparallel Greek key type d(G7) quadruplex structures with different coordinated ions, namely Na+ and K+ ion, water and Na+ counter ions, using the AMBER force field and Particle Mesh Ewald technique for electrostatic interactions. Antiparallel structures are stable during the simulation, with root mean square deviation values of ∼ 1.5 Å from the initial structures. Hydrogen bonding patterns within the G-tetrads depend on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate different cations. However, alternating syn-anti arrangement of bases along a chain as well as in a quartet is maintained through out the MD simulation. Coordinated Na+ ions, within the quadruplex cavity are quite mobile within the central channel and can even enter or exit from the quadruplex core, whereas coordinated K+ ions are quite immobile. MD studies at 400K indicate that K+ ion cannot come out from the quadruplex core without breaking the terminal G-tetrads. Smaller grooves in antiparallel structures are better binding sites for hydrated counter ions, while a string of hydrogen bonded water molecules are observed within both the small and large grooves. The hydration free energy for the K+ ion coordinated structure is more favourable than that for the Na+ ion coordinated antiparallel quadruplex structure.

Effect of Coordinated Ions on Structure and Flexibility of Parallel G-quadruplexes: A Molecular Dynamics Study

Single tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G7) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the O6 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. These quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 Å from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Na+ counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. In the absence of any coordinated ion, due to strong mutual repulsion, O6 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures.

Modeling of polyvinylpyrrolidone and polyvinylimidazole in aqueous solution

We present the results of a molecular modeling investigation of iso-, syndio-, and atactic polyvinylpyrrolidone (PVP) and polyvinylimidazole (PVI) 20-mers in aqueous and ionic solutions at ambient conditions using the AMBER force filed in conjunction with the SPC/E water model. The PVP-water and PVI-water interactions were parameterized using solution properties of monomer-analogous molecules. Simulation of isolated oligomers in aqueous solution provided the structural (pair correlation functions, coordination numbers) and dynamic (residence times) characteristics of the polymer-water ‘interface’. Analysis of the oligomer conformational statistics permitted the construction of polymer conformations in an aqueous environment and the computation of characteristic ratios and structure factors. Finally, the oligomer conformational behavior was studied in the presence of sodium benzenesulfonate using the particle mesh Ewald technique.