Christine Peter

The GROMOS software for biomolecular simulation: GROMOS05

We present the latest version of the Groningen Molecular Simulation program package, GROMOS05. It has been developed for the dynamical modelling of (bio)molecules using the methods of molecular dynamics, stochastic dynamics, and energy minimization. An overview of GROMOS05 is given, highlighting features not present in the last major release, GROMOS96. The organization of the program package is outlined and the included analysis package GROMOS++ is described. Finally, some applications illustrating the various available functionalities are presented.

Multiscale simulation of soft matter systems - from the atomistic to the coarse-grained level and back

Many physical phenomena and properties of soft matter systems such as synthetic or biological materials are governed by interactions and processes on a wide range of length- and time-scales. Computer simulation approaches that are targeted at questions in these systems require models which cover these scales and the respective levels of resolution. Multiscale simulation methods combine and systematically link several simulation hierarchies so that they can address phenomena at multiple levels of resolution. In order to reach the mesoscopic time- and length-scales important for many material properties, methods that bridge from the atomistic (microscopic) to a coarser (mesocopic) level are developed. Here, we review coarse-grained simulation models that are linked to a higher resolution atomistic description. In particular, we focus on structure-based coarse-graining methods which are used for a variety of soft matter problems – ranging from structure-formation in amorphous polymers to biomolecular aggregation. It is shown that by coarse-grained simulation in combination with an efficient backmapping methodology one can obtain well-equilibrated long time- and large length-scale atomistic structures of polymeric melts or biomolecular aggregates which can be used for comparison to experimental data. Methodological aspects are addressed such as the question of the time-scales and dynamics in the different simulation hierarchies and an outlook to future challenges in the area of resolution exchange approaches and adaptive resolution models is presented.

The Key to Solving the Protein-Folding Problem Lies in an Accurate Description of the Denatured State

Accurate simulation at the atomic level of the folding process of a variety of peptides into different native folds can be achieved with a general purpose force field and Newtons equations of motion. The key to understanding this peptide folding lies in the unexpectedly small size of the denatured state and an accurate description thereof.

Estimating entropies from molecular dynamics simulations

While the determination of free-energy differences by MD simulation has become a standard procedure for which many techniques have been developed, total entropies and entropy differences are still hardly ever computed. An overview of techniques to determine entropy differences is given, and the accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated using liquid water as a test system. Reasonably accurate entropy differences are obtained through thermodynamic integration in which many copies of a solute are desolvated. When only one solute molecule is involved, only two methods seem to yield useful results, the calculation of solute-solvent entropy through thermodynamic integration, and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference. One-step perturbation methods seem unsuitable to obtain entropy estimates.

Multiscale simulation of soft matter systems

This paper gives a short introduction to multiscale simulation approaches in soft matter science. This paper is based on and extended from a previous review. (1. C. Peter and K. Kremer, Soft Matter, 2009, DOI:10.1039/b912027k.) It also includes a discussion of aspects of soft matter in general and a short account of one of the historically underlying concepts, namely renormalization group theory. Some different concepts and several typical problems are shortly addressed, including a (more personal) view on challenges and chances.

Influence of cut-off truncation and artificial periodicity of electrostatic interactions in molecular simulations of solvated ions: A continuum electrostatics study

A new algorithm relying on finite integration is presented that solves the equations of continuum electrostatics for truncated (and possibly reaction-field corrected) solute–solvent and solvent–solvent interactions under either nonperiodic or periodic boundary conditions. After testing and validation by comparison with existing methods, the algorithm is applied to investigate the effect of cut-off truncation and artificial periodicity in explicit-solvent simulations of ionic solvation and ion–ion interactions. Both cut-off truncation and artificial periodicity significantly alter the polarization around a spherical ion and thus, its solvation free energy. The nature and magnitude of the two perturbations are analyzed in details, and correction terms are proposed for both effects. Cut-off truncation is also shown to induce strong alterations in the potential of mean force for ion–ion interaction. These observations help to rationalize artifacts previously observed in explicit–solvent simulations, namely spurious features in the radial distribution functions close to the cut-off distance and alterations in the relative stabilities of contact, solvent-separated and free ion pairs.

Self-assembling dipeptides: conformational sampling in solvent-free coarse-grained simulation

We discuss the development of a coarse-grained (CG) model for molecular dynamics (MD) simulation of a hydrophobic dipeptide, diphenylalanine, in aqueous solution. The peptide backbone is described with two CG beads per amino acid, the side groups and charged end groups are each described with one CG bead. In the derivation of interaction functions between CG beads we follow a bottom-up strategy where we devise potentials such that the resulting CG simulation reproduces the conformational sampling and the intermolecular interactions observed in an atomistic simulation of the same peptide. In the CG model, conformational flexibility of the peptide is accounted for through a set of intra-molecular (bonded) potentials. The approach followed to obtain the bonded potentials is discussed in detail. The CG potentials for nonbonded interactions are based on potentials of mean force obtained by atomistic simulations in aqueous solution. Following this approach, solvent mediation effects are included in the effective bead-bead nonbonded interactions and computationally very efficient (solvent-free) simulations of self-assembly processes can be performed. We show that the conformational properties of the all-atom dipeptide in explicit solvent can be accurately reproduced with the CG model. Moreover, preliminary simulations of peptide self-assembly performed with the CG model illustrate good agreement with results obtained from all-atom, explicit solvent simulations.

Transferability of Nonbonded Interaction Potentials for Coarse-Grained Simulations: Benzene in Water

Methods to parametrize coarse-grained simulation models for molecular fluids frequently either attempt to match the fluid structure (e.g., pair correlation functions) previously obtained with detailed atomistic models or aim at reproducing macroscopically observable thermodynamic properties. In either case, the coarse-grained models are state-point-dependent, and it is unclear to what extent the models obtained at a given state point are transferable, for example, to different compositions in the case of solution mixtures. Usually, it remains unclear as well whether structure-based potentials reproduce macroscopic thermodynamic properties and, vice versa, if thermodynamics-based potentials reproduce microscopic structural properties. In this paper, we use the Kirkwood-Buff theory of solutions in order to link local structural information and thermodynamic properties sampled with structure-based potentials. We investigate benzene/water mixtures at varying concentrations as a model hydrophobic/hydrophilic system and study the transferability of a coarse-grained model that describes the water and benzene molecules as single interaction sites. The coarse-grained model, parametrized at a high aqueous dilution of benzene, reproduces the Kirkwood-Buff integrals of mixtures obtained with the detailed-atomistic model, and it reproduces the change in the benzene chemical potential with composition up to the concentration of thermodynamic instability. The observed transferability of the potential supports the idea that hydrophobic interactions between small molecules are pairwise additive.

Self-assembling dipeptides: including solvent degrees of freedom in a coarse-grained model

In the previous paper [A. Villa, C. Peter, N. F. A. van der Vegt, Phys. Chem. Chem. Phys., 2009, DOI: ], a strategy to develop a solvent-free coarse-grained model for peptides is outlined which is based on an atomistic (force field) description. The coarse-grained model is designed such that it correctly captures the conformational flexibility of the molecules and reproduces the interaction between peptides in aqueous solution. In the present paper, we revisit this model and present a method to devise nonbonded interactions such that also the coarse-grained level maintains explicit solvent degrees of freedom. In this new approach we rely on a structure-based coarse graining methodology which preserves the solvation structure around the peptides in combination with a method to devise nonbonded potentials between peptide beads in a way that the peptide-peptide interaction in water is represented correctly and that results in the correct thermodynamic association behavior. The outlined coarse graining strategy provides us with two (one implicit- and one explicit-solvent) models that are well suited for multiscale-simulation and scale-bridging purposes. We show that this is a powerful tool to efficiently simulate long time-scale and large length-scale biomolecular processes such as peptide self-assembly. In combination with an efficient backmapping methodology we can obtain well-equilibrated atomistic structures of the resulting aggregates.

Classical simulations from the atomistic to the mesoscale and back: coarse graining an azobenzene liquid crystal

We describe the development of a coarse grained model for molecular dynamics (MD) simulations of a liquid-crystalline (LC) compound with an azobenzene mesogen. It is investigated how coarse graining methods originally developed to simulate amorphous polymeric systems can be extended to liquid crystals. The coarse grained (CG) model is constructed in a way that it allows carrying over of chemical details (i.e. the form of specific/attractive interactions) from the atomistic to the CG level, devising a new route to construct mesoscale models for liquid crystals with a close link to chemically more realistic atomistic ones. In addition it is possible to switch between the atomistic and the CG levels of resolution on demand through an inverse mapping procedure. By this we obtain representative large-scale atomistic coordinates based on CG structures and long-time atomistic trajectories generated from CG mesoscale simulations.