Search PubMed⌕ Search

Biomedical subjects

Herman J C Berendsen

Publications and source records attributed to Herman J C Berendsen.

10 recordsLinked to original sources
PubMed2005

Calculation of the redox potential of the protein azurin and some mutants.

Azurin from Pseudomonas aeruginosa is a small 128-residue, copper-containing protein. Its redox potential can be modified by mutating the protein. Free-energy calculations based on classical molecular-dynamics simulations of the protein and from mutants in aqueous solution at different pH values were used to compute relative redox potentials. The precision of the free-energy calculations with the lambda coupling-parameter approach is evaluated as function of the number and sequence of lambda values, the sampling time and initial conditions. It is found that the precision is critically dependent on the relaxation of hydrogen-bonding networks when changing the atomic-charge distribution due to a change of redox state or pH value. The errors in the free energies range from 1 to 10 k(B)T, depending on the type of process. Only qualitative estimates of the change in redox potential by protein mutation can be obtained.

Amino Acid Substitution↗
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

Signal transduction in the photoactive yellow protein. II. Proton transfer initiates conformational changes.

Molecular dynamics simulation techniques, together with semiempirical PM3 calculations, have been used to investigate the effect of photoisomerization of the 4-hydroxy-cinnamic acid chromophore on the structural properties of the photoactive yellow protein (PYP) from Ectothiorodospira halophila. In this bacteria, exposure to blue light leads to a negative photoactic response. The calculations suggest that the isomerization does not directly destabilize the protein. However, because of the isomerization, a proton transfer from a glutamic acid residue (Glu46) to the phenolate oxygen atom of the chromophore becomes energetically favorable. The proton transfer initiates conformational changes within the protein, which are in turn believed to lead to signaling.

Bacterial Proteins↗
PubMed2002

Signal transduction in the photoactive yellow protein. I. Photon absorption and the isomerization of the chromophore.

Molecular dynamics simulation techniques together with time-dependent density functional theory calculations have been used to investigate the effect of photon absorption by a 4-hydroxy-cinnamic acid chromophore on the structural properties of the photoactive yellow protein (PYP) from Ectothiorodospira halophila. The calculations suggest that the protein not only modifies the absorption spectrum of the chromophore but also regulates the subsequent isomerization of the chromophore by stabilizing the isomerization transition state. Although signaling from PYP is thought to involve partial unfolding of the protein, the mechanical effects accompanying isomerization do not appear to directly destabilize the protein.

Bacterial Proteins↗
PubMed2002

Order-parameter tensor description of HPr in a medium of oriented bicelles.

Residual dipolar couplings between 15N and 1H nuclear spins in HPr were used to determine the protein's orientation in a medium of bicelles, oriented by a magnetic field. In the case of wild-type HPr the protein's non-spherical shape can explain its orientation in this medium. In the case of the F48W mutant it was found that at least one other mechanism contributes to the observed orientation of the protein, to a degree that depends on the concentration of phosphate ions in the medium. We propose that the F48W mutant has a weak affinity towards the bicelle-surfaces that decreases with increasing phosphate concentrations. We used an order-parameter description to analyse this situation and to determine the axis of main order and the sign of the order parameter pertaining to this additional orientation mechanism.

Anisotropy↗
PubMed2002

Molecular dynamics simulations as a tool for improving protein stability.

Haloalkane dehalogenase (DhlA) was used as a model protein to explore the possibility to use molecular dynamics (MD) simulations as a tool to identify flexible regions in proteins that can serve as a target for stability enhancement by introduction of a disulfide bond. DhlA consists of two domains: an alpha/beta-hydrolase fold main domain and a cap domain composed of five alpha-helices. MD simulations of DhlA showed high mobility in a helix-loop-helix region in the cap domain, involving residues 184-211. A disulfide cross-link was engineered between residue 201 of this flexible region and residue 16 of the main domain. The mutant enzyme showed substantial changes in both thermal and urea denaturation. The oxidized form of the mutant enzyme showed an increase of the apparent transition temperature from 47.5 to 52.5 degrees C, whereas the T(m,app) of the reduced mutant decreased by more than 8 degrees C compared to the wild-type enzyme. Urea denaturation results showed a similar trend. Measurement of the kinetic stability showed that the introduction of the disulfide bond caused a decrease in activation free energy of unfolding of 0.43 kcal mol(-1) compared to the wild-type enzyme and also indicated that the helix-loop-helix region was involved early in the unfolding process. The results show that MD simulations are capable of identifying mobile protein domains that can successfully be used as a target for stability enhancement by the introduction of a disulfide cross-link.

Computer Simulation↗