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.

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GROMACS: Fast, flexible, and free

A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine containing head groups and with both saturated and unsaturated aliphatic chains. Motivated by the current CHARMM lipid FF (C27 and C27r) systematically yielding values of the surface area per lipid that are smaller than experimental estimates and gel-like structures of bilayers well above the gel transition temperature, selected torsional, Lennard-Jones and partial atomic charge parameters were modified by targeting both quantum mechanical (QM) and experimental data. QM calculations ranging from high-level ab initio calculations on small molecules to semiempirical QM studies on a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer in combination with experimental thermodynamic data were used as target data for parameter optimization. These changes were tested with simulations of pure bilayers at high hydration of the following six lipids: ...

Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types

Structure of lipid bilayers

On laboratory time scales, the energy landscape of a weak bond along a dissociation pathway is fully explored through Brownian-thermal excitations, and energy barriers become encoded in a dissociation time that varies with applied force. Probed with ramps of force over an enormous range of rates (force/time), this kinetic profile is transformed into a dynamic spectrum of bond rupture force as a function of loading rate. On a logarithmic scale in loading rate, the force spectrum provides an easy-to-read map of the prominent energy barriers traversed along the force-driven pathway and exposes the differences in energy between barriers. In this way, the method of dynamic force spectroscopy (DFS) is being used to probe the complex relation between force-lifetime-and chemistry in single molecular bonds. Most important, DFS probes the inner world of molecular interactions to reveal barriers that are difficult or impossible to detect in assays of near equilibrium dissociation but that determine bond lifetime and strength under rapid detachment. To use an ultrasensitive force probe as a spectroscopic tool, we need to understand the physics of bond dissociation under force, the impact of experimental technique on the measurement of detachment force (bond strength), the consequences of complex interactions in macromolecular bonds, and effects of multiply-bonded attachments.

Probing the Relation Between Force—Lifetime—and Chemistry in Single Molecular Bonds

Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying molecular mechanisms remain unknown. Here we show experimentally and theoretically that pristine graphene and graphene oxide nanosheets can induce the degradation of the inner and outer cell membranes of Escherichia coli, and reduce their viability. Transmission electron microscopy shows three rough stages, and molecular dynamics simulations reveal the atomic details of the process. Graphene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid molecules. This destructive extraction offers a novel mechanism for the molecular basis of graphene's cytotoxicity and antibacterial activity.

Oliver Berger

Papers

Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature.

Adhesion Forces of Lipids in a Phospholipid Membrane Studied by Molecular Dynamics Simulations

Structure and fluctuations of bacteriorhodopsin in the purple membrane: a molecular dynamics study.

Gene cloning and cellular localization of a membrane-bound acid phosphatase of Leishmania mexicana