Biomedical subjects

Berk Hess

Publications and source records attributed to Berk Hess.

10 recordsLinked to original sources

PubMed2006

Hydration thermodynamic properties of amino acid analogues: a systematic comparison of biomolecular force fields and water models.

We present an extensive study on hydration thermodynamic properties of analogues of 13 amino acid side chains at 298 K and 1 atm. The hydration free energies DeltaG, entropies DeltaS, enthalpies DeltaH, and heat capacities Deltac(P)() were determined for 10 combinations of force fields and water models. The statistical sampling was extended such that precisions of 0.3, 0.8, 0.8 kJ/mol and 25 J/(mol K) were reached for DeltaG, TDeltaS, DeltaH, and Deltac(P)(), respectively. The three force fields used in this study are AMBER99, GROMOS 53A6, and OPLS-AA; the five water models are SPC, SPC/E, TIP3P, TIP4P, and TIP4P-Ew. We found that the choice of water model strongly influences the accuracy of the calculated hydration entropies, enthalpies, and heat capacities, while differences in accuracy between the force fields are small. On the basis of an analysis of the hydrophobic analogues of the amino acid side chains, we discuss what properties of the water models are responsible for the observed discrepancies between computed and experimental values. The SPC/E water model performs best with all three biomolecular force fields.

Journal Article↗

PubMed2006

Density functional study of ion hydration for the alkali metal ions (Li+, Na+, K+) and the halide ions (F-, Br-, Cl-).

We performed first principles density functional calculations to study the effect of monovalent ions M+ (M = Li,Na,K) and A- (A = F,Cl,Br) in water with the aim of characterizing the local molecular properties of hydration. For this reason, several ion-water clusters, up to five or six water molecules were considered; such structures were optimized, and the Wannier analysis was then applied to determine the average molecular dipole moment of water. We found that with an increasing number of water molecules, the molecular polarization is determined by the water-water interaction rather than the water-ion interaction, as one would intuitively expect. These results are consistent with those obtained in previous density functional calculations and with other results obtained by employing classical polarizable water models. The main message of this work is that as one increases the number of molecules the average dipole moment of all water molecules and the ones in the first shell tends to the same value as the average of a similar sized cluster of pure water. This supports the use of nonpolarizable classical models of water in classical atomistic simulations.

Bromine↗

PubMed2006

Osmotic coefficients of atomistic NaCl (aq) force fields.

Solvated ions are becoming increasingly important for (bio)molecular simulations. But there are not much suitable data to validate the intermediate-range solution structure that ion-water force fields produce. We compare six selected combinations of four biomolecular Na-Cl force fields and four popular water models by means of effective ion-ion potentials. First we derive an effective potential at high dilution from simulations of two ions in explicit water. At higher ionic concentration multibody effects will become important. We propose to capture those by employing a concentration dependent dielectric permittivity. With the so obtained effective potentials we then perform implicit solvent simulations. We demonstrate that our effective potentials accurately reproduce ion-ion coordination numbers and the local structure. They allow us furthermore to calculate osmotic coefficients that can be directly compared with experimental data. We show that the osmotic coefficient is a sensitive and accurate measure for the effective ion-ion interactions and the intermediate-range structure of the solution. It is therefore a suitable and useful quantity for validating and parametrizing atomistic ion-water force fields.

Journal Article↗

PubMed2006

Modeling multibody effects in ionic solutions with a concentration dependent dielectric permittivity.

We report a new strategy to parametrize effective ion-ion potentials for implicit solvent simulations of charged systems. The effective potential includes a pair term and a Coulomb term that by means of a concentration dependent dielectric permittivity takes into account multibody effects. We demonstrate that this approach allows us to accurately reproduce the solution osmotic properties and the ion coordination up to concentrations of 2.8 M aqueous NaCl.

Journal Article↗

PubMed2005

Reproducible polypeptide folding and structure prediction using molecular dynamics simulations.

The folding of a polypeptide from an extended state to a well-defined conformation is studied using microsecond classical molecular dynamics (MD) simulations and replica exchange molecular dynamics (REMD) simulations in explicit solvent and in vacuo. It is shown that the solvated peptide folds many times in the REMD simulations but only a few times in the conventional simulations. From the folding events in the classical simulations we estimate an approximate folding time of 1-2 micros. The REMD simulations allow enough sampling to deduce a detailed Gibbs free energy landscape in three dimensions. The global minimum of the energy landscape corresponds to the native state of the peptide as determined previously by nuclear magnetic resonance (NMR) experiments. Starting from an extended state it takes about 50 ns before the native structure appears in the REMD simulations, about an order of magnitude faster than conventional MD. The calculated melting curve is in good qualitative agreement with experiment. In vacuo, the peptide collapses rapidly to a conformation that is substantially different from the native state in solvent.

Computer Simulation↗

PubMed2005

GROMACS: fast, flexible, and free.

This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is http://www.gromacs.org.

Algorithms↗

PubMed2004

An application of flexible constraints in Monte Carlo simulations of the isobaric--isothermal ensemble of liquid water and ice Ih with the polarizable and flexible mobile charge densities in harmonic oscillators model.

The method of flexible constraints was implemented in a Monte Carlo code to perform numerical simulations of liquid water and ice Ih in the constant number of molecules, volume, and temperature and constant pressure, instead of volume ensembles, using the polarizable and flexible mobile charge densities in harmonic oscillators (MCDHO) model. The structural and energetic results for the liquid at T=298 K and rho=997 kg m(-3) were in good agreement with those obtained from molecular dynamics. The density obtained at P=1 atm with flexible constraints, rho=1008 kg m(-3), was slightly lower than with the classical sampling of the intramolecular vibrations, rho=1010 kg m(-3). The comparison of the structures and energies found for water hexamers and for ice Ih with six standard empirical models to those obtained with MCDHO, show this latter to perform better in describing water far from ambient conditions: the MCDHO minimum lattice energy, density, and lattice constants were in good agreement with experiment. The average angle HOH of the water molecule in ice was predicted to be slightly larger than in the liquid, yet 1.2% smaller than the experimental value.

Journal Article↗

PubMed2004

Photoactivation of the photoactive yellow protein: why photon absorption triggers a trans-to-cis Isomerization of the chromophore in the protein.

Atomistic QM/MM simulations have been carried out on the complete photocycle of Photoactive Yellow Protein, a bacterial photoreceptor, in which blue light triggers isomerization of a covalently bound chromophore. The "chemical role" of the protein cavity in the control of the photoisomerization step has been elucidated. Isomerization is facilitated due to preferential electrostatic stabilization of the chromophore's excited state by the guanidium group of Arg52, located just above the negatively charged chromophore ring. In vacuo isomerization does not occur. Isomerization of the double bond is enhanced relative to isomerization of a single bond due to the steric interactions between the phenyl ring of the chromophore and the side chains of Arg52 and Phe62. In the isomerized configuration (ground-state cis), a proton transfer from Glu46 to the chromophore is far more probable than in the initial configuration (ground-state trans). It is this proton transfer that initiates the conformational changes within the protein, which are believed to lead to signaling.

Animals↗

PubMed2002

Convergence of sampling in protein simulations.

With molecular dynamics protein dynamics can be simulated in atomic detail. Current computers are not fast enough to probe all available conformations, but fluctuations around one conformation can be sampled to a reasonable extent. The motions with the largest fluctuations can be filtered out of a simulation using covariance or principal component analysis. A problem with this analysis is that random diffusion can appear as correlated motion. An analysis is presented of how long a simulation should be to obtain relevant results for global motions. The analysis reveals that the cosine content of the principal components is a good indicator for bad sampling.

Algorithms↗

PubMed2002

Analysis and evaluation of channel models: simulations of alamethicin.

Alamethicin is an antimicrobial peptide that forms stable channels with well-defined conductance levels. We have used extended molecular dynamics simulations of alamethicin bundles consisting of 4, 5, 6, 7, and 8 helices in a palmitoyl-oleolyl-phosphatidylcholine bilayer to evaluate and analyze channel models and to link the models to the experimentally measured conductance levels. Our results suggest that four helices do not form a stable water-filled channel and might not even form a stable intermediate. The lowest measurable conductance level is likely to correspond to the pentamer. At higher aggregation numbers the bundles become less symmetrical. Water properties inside the different-sized bundles are similar. The hexamer is the most stable model with a stability comparable with simulations based on crystal structures. The simulation was extended from 4 to 20 ns or several times the mean passage time of an ion. Essential dynamics analyses were used to test the hypothesis that correlated motions of the helical bundles account for high-frequency noise observed in open channel measurements. In a 20-ns simulation of a hexameric alamethicin bundle, the main motions are those of individual helices, not of the bundle as a whole. A detailed comparison of simulations using different methods to treat long-range electrostatic interactions (a twin range cutoff, Particle Mesh Ewald, and a twin range cutoff combined with a reaction field correction) shows that water orientation inside the alamethicin channels is sensitive to the algorithms used. In all cases, water ordering due to the protein structure is strong, although the exact profile changes somewhat. Adding an extra 4-nm layer of water only changes the water ordering slightly in the case of particle mesh Ewald, suggesting that periodicity artifacts for this system are not serious.

Alamethicin↗