# Herman J C BerendsenUniversity of Groningen | RUG · Groningen Biomolecular Sciences and Biotechnology Institute (GBB)

Herman J C Berendsen

Prof. Dr. (Emiritus)

## About

316

Publications

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145,110

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Introduction

I am emeritus professor at the University of Groningen, interested in molecular dynamics. See www.hjcb.nl.

Additional affiliations

Education

September 1959 - October 1962

September 1950 - September 1957

## Publications

Publications (316)

The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic downshock. Sensing bilayer tension, MscL channels are sensitive to changes in the bilayer environment and are, therefore, an ideal test case for exploring membrane protein coupling. H...

In multiscale molecular dynamics simulations the accuracy of detailed models is combined with the efficiency of a reduced representation. For several applications — namely those of sampling enhancement — it is desirable to combine fine-grained (FG) and coarse-grained (CG) approaches into a single hybrid approach with an adjustable mixing parameter....

ABSTRACT: In this paper we discuss thermostatting using stochastic
methods for molecular simulations where constraints are present. For socalled
impulsive thermostats, like the Andersen thermostat, the equilibrium
temperature will differ significantly from the imposed temperature when a
limited number of particles are picked and constraints are app...

GROMACS (GROningen MAchine for Chemical Simulations) is a molecular dynamics package primarily designed for simulations of proteins, lipids and nucleic acids. It was originally developed in the Biophysical Chemistry department of University of Groningen, and is now maintained by contributors in universities and research centers across the world.

The mechanosensitive channels of large conductance (MscL) are bacterial membrane proteins that serve as last resort emergency release valves in case of severe osmotic down shock. The channels activate with applied bilayer tension, opening a large (ca. 3 nS) mostly unselective pore. Among the mechanosensitive channels, MscL is the most studied and o...

Presents the parallelization of a new algorithm - thermostat - for molecular dynamics simulations. It should be taken into account that molecular dynamics simulations are time consuming. In some cases the running time varies from days to weeks and even months. Therefore, parallelization is one solution for reducing the execution time. The abstract...

Multiscale modeling is a recent approach to simulating molecular systems, such as membranes and liposomes, in which different levels of detail are combined. By using distinct models, it is often possible to speed up or enrich the sampling of a given system. Examples are the use in molecular dynamics simulations of both coarse-grained and fine-grain...

In this article, we present several algorithms for stochastic dynamics, including Langevin dynamics and different variants of Dissipative Particle Dynamics (DPD), applicable to systems with or without constraints. The algorithms are based on the impulsive application of friction and noise, thus avoiding the computational complexity of algorithms th...

With today's available computer power, free energy calculations from equilibrium molecular dynamics simulations "via counting" become feasible for an increasing number of reactions. An example is the dimerization reaction of transmembrane alpha-helices. If an extended simulation of the two helices covers sufficiently many dimerization and dissociat...

Molecular Dynamics computer simulations have been carried out both on simplified model systems of biological membranes and
on di(palmitoyl)lecithin/water multibilayers. The results, which agree with experimental data on chain order parameters, show
a considerable disorder with atomic distributions extending over a region of about 0.8 nm. The lecith...

All students taking laboratory courses within the physical sciences and engineering will benefit from this book, whilst researchers will find it an invaluable reference. This concise, practical guide brings the reader up-to-speed on the proper handling and presentation of scientific data and its inaccuracies. It covers all the vital topics with pra...

The simulation of physical systems requires a simplified, hierarchical approach which models each level from the atomistic to the macroscopic scale. From quantum mechanics to fluid dynamics, this book systematically treats the broad scope of computer modeling and simulations, describing the fundamental theory behind each level of approximation. Ber...

The simulation of physical systems requires a simplified, hierarchical approach which models each level from the atomistic to the macroscopic scale. From quantum mechanics to fluid dynamics, this book systematically treats the broad scope of computer modeling and simulations, describing the fundamental theory behind each level of approximation. Ber...

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 n...

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 p...

The water relaxation rates of several flavoproteins in the semiquinone state have been investigated by the spin echo technique. The results indicate a rather unspecific interaction between water and the protein-bound flavosemiquinones. An average interaction distance of 0.3-0.5 nm has been estimated. From the temperature dependence of the rate cons...

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 st...

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...

We have studied, by means of molecular dynamics (MD) simulations, the effect of two hydrophobic cosolutes, tert-butanol (t-BuOH) and ethanol (EtOH), on the neutral hydrolysis of p-methoxyphenyl dichloroacetate (MPDA) in water. Shifts were calculated in a pre-equilibrium, defined as a spatial distribution of the reacting molecules satisfying specifi...

A molecular model for urea to be used in conjunction with the simple point charge (SPC) model for liquid water in protein denaturation studies is validated by comparison of molecular dynamics (MD) simulation results to experimental data at 298 K as a function of urea mole fraction. The density, enthalpy of mixing, free enthalpy of urea hydration, a...

A report of the inter-union bioinformatics group.

Action must be taken now to ensure that data are safely archived and always accessible.

A method is presented to refine models built by homology by the use of restricted molecular dynamics (MD) techniques. The basic idea behind this method is the use of structure validation software to determine for each residue the likelihood that it is modeled correctly. This information is used to determine constraints and restraints in an MD simul...

Molecular dynamics (MD) simulations and polarized subnanosecond time-resolved flavin fluorescence spectroscopy have been used to study the conformational dynamics of the flavin adenine dinucleotide (FAD) cofactor in aqueous solution. FAD displays a highly heterogeneous fluorescence intensity decay, resulting in lifetime spectra with two major compo...

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 mech...

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 p...

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 n...

In classical molecular simulations chemical bonds and bond angles have been modeled either as rigid constraints, or as nearly harmonic oscillators. However, neither model is a good description of a chemical bond, which is a quantum oscillator that in most cases occupies the ground state only. A quantum oscillator in the ground state can be represen...

Introduction Interesting motions in biomolecular systems, such as proteins and nucleic acids in solution and bilayer membranes, occur on a time scale usually far beyond the range accessible to molecular dynamics (MD) simulations. While MD simulations of fully hydrated systems comprising tens of thousands of atoms are now possible in the range of te...

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...

Decades of method development and increasing computational power are enabling researchers to simulate complex biological processes in real time. In his Perspective, [Berendsen][1] highlights the report by [de Groot and GrubmA¼ller][2], who simulate the permeation of water through the membrane-channel protein aquaporin-1 at atomic resolution. Simula...

One of the ingredients in Granular Dynamics (or DEM) is a description of interparticle forces. In this paper the effect of surface roughness on Hamaker and liquid bridge interactions is investigated. Three different models are used (excluded volume, stochastic roughness and explicit asperities). In general, the latter two give similar results. Roug...

The application of cutinase from Fusarium solani pisi as a fat-stain removing ingredient in laundry washing is hampered by its lack of stability in the presence of anionic surfactants. We postulate that the stability of cutinase towards anionics can be improved by mutations increasing its temperature stability. Thermal unfolding as measured with DS...

The European Science Foundation SIMU programme aimed at building cooperation across Europe in the field of computational physics and chemistry of condensed matter, with particular emphasis on the development of novel computational techniques to perform multiscale molecular simulations. Articles in this issue include: 1. Order from Disorder - Entrop...

The design of a transmembrane four-helix bundle is described. We start with an idealized four-helix bundle geometry, then use statistical information to build a plausible transmembrane bundle. Appropriate residues are chosen using database knowledge on the sequences of membrane helices and loops, then the packing of the bundle core is optimized, an...

Understanding the binding and insertion of peptides in lipid bilayers is a prerequisite for understanding phenomena such as antimicrobial activity and membrane-protein folding. We describe molecular dynamics simulations of the antimicrobial peptide alamethicin in lipid/water and octane/water environments, taking into account an external electric fi...

In this work we present a new proposal to model intermolecular interactions and use it for water molecules. The parameters of the model were fitted to reproduce the single molecule’s electrostatic properties, a sample of 352 points in a refined ab initio single molecule deformation potential energy surface (PES), and the theoretical limit of the di...

We simulated micelles of 40 (M40), 54 (M54), and 65 (M65) dodecylphosphocholine (DPC) lipids in water for up to 15 ns and analyzed the system energetics, structure of the water/lipid interface, structure and dynamics of the lipid tails, and overall size and shape of the micelles. M54 and M65 are similar, being mostly spherical in shape with compara...

Several techniques for the analysis of the internal motions of proteins are available - separating large collective motions from small, presumably uninteresting motions. Such descriptions are helpful in the characterization of internal motions and provide insight into the energy landscape of proteins. The real challenge, however, is to relate large...

Human choriogonadotropin (hCG) belongs to a family of heterodimeric glycoprotein hormones involved in reproduction. Over 75 ns of molecular dynamics simulations of this heterodimer and the free subunit were performed and validated by experimental information to arrive at a qualitative dynamical description of these molecules. A number of 5-ns simul...

In this article the quasi-Gaussian entropy theory is derived for pure quantum systems, along the same lines as previously done for semi-classical systems. The crucial element for the evaluation of the Helmholtz free energy and its temperature dependence is the moment generating function of the discrete probability distribution of the quantum mechan...

In this article we present an equation of state for fluids, based on the quasi-Gaussian entropy theory. The temperature dependence along isochores is described by a confined Gamma state, previously introduced, combined with a simple perturbation term. The eleven parameters occurring in the free energy and pressure expressions along the isochores ar...

The structural and dynamical behavior of the 41-56 beta-hairpin from the protein G B1 domain (GB1) has been studied at different temperatures using molecular dynamics (MD) simulations in an aqueous environment. The purpose of these simulations is to establish the stability of this hairpin in view of its possible role as a nucleation site for protei...

Alamethicin is an amphipathic alpha-helical peptide that forms ion channels. An early event in channel formation is believed to be the binding of alamethicin to the surface of a lipid bilayer. Molecular dynamics simulations are used to compare the structural and dynamic properties of alamethicin in water and alamethicin bound to the surface of a ph...

A systematic analysis is performed on the effectiveness of removing degrees of freedom from hydrogen atoms and/or increasing hydrogen masses to increase the efficiency of molecular dynamics simulations of hydrogen-rich systems such as proteins in water. In proteins, high-frequency bond-angle vibrations involving hydrogen atoms limit the time step t...

The dynamics of collective protein motions derived from Molecular Dynamics simulations have been studied for two small model proteins: initiation factor I and the B1 domain of Protein G. First, we compared the structural fluctuations, obtained by local harmonic approximations in different energy minima, with the ones revealed by large scale molecul...

By computer simulation, using both quantum and classical dynamics, we determined the rate constant and the kinetic isotope effect of the rate-determining step in the neutral hydrolysis of p-methoxyphenyl dichloroacetate in aqueous solution. This step involves a proton transfer concerted with the formation of a CO bond. A method of biased sampling w...

A systematic analysis is performed on the effectiveness of removing degrees of freedom from hydrogen atoms and/or increasing hydrogen masses to increase the efficiency of molecular dynamics simulations of hydrogen-rich systems such as proteins in water. In proteins, high-frequency bond-angle vibrations involving hydrogen atoms limit the time step t...

We present the results of 2-ns molecular dynamics (MD) simulations of a hexameric bundle of Alm helices in a 1-palmitoyl-2-oleoylphosphatidylcholine bilayer. These simulations explore the dynamic properties of a model of a helix bundle channel in a complete phospholipid bilayer in an aqueous environment. We explore the stability and conformational...

The dynamics of collective protein motions derived from Molecular Dynamics simulations have been studied for two small model proteins: initiation factor I and the B1 domain of Protein G. First, we compared the structural fluctuations, obtained by local harmonic approximations in different energy minima, with the ones revealed by large scale molecul...

Conformational changes are known to play a crucial role in the function of the bacterial GroE chaperonin system. Here, results are presented from an essential dynamics analysis of known experimental structures and from computer simulations of GroEL using the CONCOORD method. The results indicate a possible direct form of inter-ring communication as...

this paper we will however mostly refer to them simply as domains.

Alamethicin is a 20-residue channel-forming peptide that forms a stable amphipathic alpha-helix in membrane and membrane-mimetic environments. This helix contains a kink induced by a central Gly-X-X-Pro sequence motif. Alamethicin channels are activated by a cis positive transbilayer voltage. Channel activation is suggested to correspond to voltage...

Alamethicin is an alpha-helical channel-forming peptide, which inserts into lipid bilayers in a voltage-dependent, asymmetrical fashion. Nanosecond molecular dynamics simulations have been used to compare alamethicin conformation and dynamics in three different environments: 1) in water; 2) in methanol; and 3) inserted into a lipid (palmitoyl-oleoy...

Molecular dynamics simulations allow a direct study of the structure and dynamics of membrane proteins and lipids. We describe the behavior of aromatic residues and lipid properties in POPE and POPC bilayer models with the Escherichia coli OmpF trimer, single alamethicin and Influenza M2 helices, 4-helix M2 bundles, and two alamethicin 6-helix chan...

Several series of site-directed mutations in thermolysin-like proteases are presented that show remarkable nonadditivity in their effect on thermal stability. A simple model is proposed that relates this nonadditivity to the occurrence of independent partial unfolding processes that occur in parallel at elevated temperatures. To prove this model, a...

This article reviews the present state of Molecular Dynamics (MD) simulations and tries to give an outlook into future developments. First an overview is given of methods, algorithms and force fields. After considering the limitations of the standard present-day techniques, developments that reach beyond the present limitations are considered. Thes...

The implementation of cutinase from Fusarium solani pisi as a fat-stain removing ingredient in laundry washing is hampered by its unfolding in the presence of anionic surfactants. In this work we present molecular dynamics (MD) computer simulations on cutinase and analysis procedures to distinguish the movements related to its functional behavior (...

The implementation of cutinase from Fusarium solani pisi as a fat-stain removing ingredient in laundry washing is hampered by its unfolding in the presence of anionic surfactants. In this work we present molecular dynamics (MD) computer simulations on cutinase and analysis procedures to distinguish the movements related to its functional behavior (...

Molecular dynamics simulations allow a direct study of the structure and dynamics of membrane proteins and lipids. We describe the behavior of aromatic residues and lipid properties in POPE and POPC bilayer models with the E. coli OmpF trimer, single alamethicin and Influenza M2 helices, 4-helix M2 bundles and two alamethicin 6-helix channel models...

In previous articles we derived and tested the quasi-Gaussian entropy theory, a description of the excess Helmholtz free energy in terms of the potential energy distribution, instead of the configurational partition function. We obtained in this way the temperature dependence of thermodynamic functions in the canonical ensemble assuming a Gaussian,...

Every protein is folded in its "native" state. How the sequence of amino acids determines the folding conformation is an open question in biochemistry. Because of the huge number of possible foldings, computer simulation of the problem has been impossible. In his Perspective, Berendsen discusses results reported in the same issue by [Duan and Kollm...

The quasi-Gaussian entropy theory has been applied to reproduce the temperature dependence of the internal energy, pressure and isochoric heat capacity of a molecular dynamics simulated Lennard-Jones (LJ) fluid at density ρ = 1 (reduced units). The results show that the gamma state level of the theory is an excellent approximation, able to predict...

In previous articles we derived and tested the quasi-Gaussian entropy theory, a description of the excess free energy in terms of the potential or full internal energy or enthalpy probability distribution, instead of the (configurational) partition function. We obtained in this way the temperature dependence of thermodynamic functions in the NVT, N...

In this paper we study the properties of pores formed by OmpF porin from Escherichia coli, based on a molecular dynamics simulation of the OmpF trimer, 318 palmitoyl-oleoyl-phosphatidylethanolamine lipids, 27 Na+ ions, and 12,992 water molecules. After equilibration and a nanosecond production run, the OmpF trimer exhibits a C-alpha root mean squar...

We have performed long molecular dynamics simulations of water using four popular water models, namely simple point charge (SPC), extended simple point charge (SPC/E), and the three point (TIP3P) and four point (TIP4P) transferable intermolecular potentials. System sizes of 216 and 820 molecules were used to study the dependence of properties on th...

Molecular dynamics simulations have been carried out for Sr2+ in methanol using different Sr2+ Lennard-Jones parameters and methanol models. X-ray absorption fine structure (EXAFS) spectroscopy has been employed to assess the reliability of the ion-ion and ion-methanol potential functions used in the simulations. Radial distribution functions of Sr...

A comparison of a series of extended molecular dynamics (MD) simulations of bacteriophage T4 lysozyme in solvent with X-ray data is presented. Essential dynamics analyses were used to derive collective fluctuations from both the simulated trajectories and a distribution of crystallographic conformations. In both cases the main collective fluctuatio...

The attachment protein G of respiratory syncytial virus (RSV) has a modular architecture. The ectodomain of the protein comprises a small folded conserved region which is bounded by two mucin-like regions. In this study, a sequence and structural homology is described between this central conserved region of RSV-G and the fourth subdomain of the 55...

In this article we present a new LINear Constraint Solver (LINCS) for molecular simulations with bond constraints. The algorithm is inherently stable, as the constraints themselves are reset instead of derivatives of the constraints, thereby eliminating drift. Although the derivation of the algorithm is presented in terms of matrices, no matrix mat...