NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu.

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Scalable molecular dynamics with NAMD

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Scalable Molecular Dynamics with NAMD

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

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CHARMM: the biomolecular simulation program.

The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3-phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform "all-CHARMM" simulations on drug-target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems.

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CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.

CHARMM is an academic research program used widely for macromolecular mechanics and dynamics with versatile analysis and manipulation tools of atomic coordinates and dynamics trajectories. CHARMM-GUI, http://www.charmm-gui.org, has been developed to provide a web-based graphical user interface to generate various input files and molecular systems to facilitate and standardize the usage of common and advanced simulation techniques in CHARMM. The web environment provides an ideal platform to build and validate a molecular model system in an interactive fashion such that, if a problem is found through visual inspection, one can go back to the previous setup and regenerate the whole system again. In this article, we describe the currently available functional modules of CHARMM-GUI Input Generator that form a basis for the advanced simulation techniques. Future directions of the CHARMM-GUI development project are also discussed briefly together with other features in the CHARMM-GUI website, such as Archive and Movie Gallery.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcc.20945

CHARMM-GUI: a web-based graphical user interface for CHARMM.

A new method for performing molecular dynamics simulations under constant pressure is presented. In the method, which is based on the extended system formalism introduced by Andersen, the deterministic equations of motion for the piston degree of freedom are replaced by a Langevin equation; a suitable choice of collision frequency then eliminates the unphysical ‘‘ringing’’ of the volume associated with the piston mass. In this way it is similar to the ‘‘weak coupling algorithm’’ developed by Berendsen and co‐workers to perform molecular dynamics simulation without piston mass effects. It is shown, however, that the weak coupling algorithm induces artifacts into the simulation which can be quite severe for inhomogeneous systems such as aqueous biopolymers or liquid/liquid interfaces.

Constant pressure molecular dynamics simulation: The Langevin piston method

Statistical ensembles for simulating liquid interfaces at constant pressure and/or surface tension are examined, and equations of motion for molecular dynamics are obtained by various extensions of the Andersen extended system approach. Valid ensembles include: constant normal pressure and surface area; constant tangential pressure and length normal to the interface; constant volume and surface tension; and constant normal pressure and surface tension. Simulations at 293 K and 1 atm normal pressure show consistent results with each other and with a simulation carried out at constant volume and energy. Calculated surface tensions for octane/water (61.5 dyn/cm), octane/vacuum (20.4 dyn/cm) and water/vacuum (70.2 dyn/cm) are in very good agreement with experiment (51.6, 21.7, and 72.8 dyn/cm, respectively). The practical consequences of simulating with two other approaches commonly used for isotropic systems are demonstrated on octane/water: applying equal normal and tangential pressures leads to an instabil...

Computer simulation of liquid/liquid interfaces. I. Theory and application to octane/water

Molecular dynamics simulations of a fluid-phase dipalmitoyl phosphatidylcholine lipid bilayer in water and of neat hexadecane are reported and compared with nuclear magnetic resonance spin-lattice relaxation and quasi-elastic neutron scattering data. On the 100-picosecond time scale of the present simulations, there is effectively no difference in the reorientational dynamics of the carbons in the membrane interior and in pure hexadecane. Given that the calculated fast reorientational correlation times and the "microscopic" lateral diffusion of the lipids show excellent agreement with the experimental results, it is concluded that the apparently high viscosity of the membrane is more closely related to molecular interactions on the surface rather than in the interior.

https://science.sciencemag.org/content/sci/262/5131/223.full.pdf

Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity

A constant normal pressure‐surface tension algorithm for molecular dynamics simulation, developed in the preceding paper, was used to laterally expand and compress the surface area of a dipalmitoylphosphatidylcholine (DPPC) lipid bilayer. Then, from simulations carried out at constant normal pressure and surface area, values of the surface tension and other thermodynamic variables such as the internal energy and system volume were determined at four different values of the surface area per lipid, 60.0, 65.1, 68.1, and 72.1 A2. The surface tension shows dramatic variations with area, going from 6 to 60 dyn/cm at areas per molecule of 65.1 and 68.1 A2, respectively. An approximate thermodynamic analysis indicates that an area of 68.1 A2/lipid is the closest of the four to the free energy minimum for this system, in agreement with experimental measurements. The effect of surface area changes on the calculated deuterium order parameters, which can be compared with those obtained from nuclear magnetic resonanc...

https://www.physics.iitm.ac.in/~iol/lecture_notes/vani/general-lipid-stuff/Feller_surface_tension_1995.pdf

Computer simulation of liquid/liquid interfaces. II. Surface tension-area dependence of a bilayer and monolayer

Molecular dynamics simulations of neat octane, dodecane, hexadecane, and eicosane at 323 K are compared with experiment and analyzed with respect to terms that contribute to reorientational relaxation of CH vectors. Agreement with experiment for translational diffusion constants and rotational relaxational times is excellent. It is found that gauche−trans isomerization rates, while weakly dependent on chain position, are essentially independent of chain length and, hence, shear viscosity. In contrast, rotational correlation times of the symmetry (or “long”) axis of the instantaneous moment of inertia tensor increase monotonically with chain length, and, taking the shape dependence into account with a hydrodynamic cylinder model, are proportional to viscosity. Rotation about the long axis is strongly coupled with isomerization. Using an approximate separation of internal and overall motion, reorientation of octane is shown to be largely “rigid body”. For the central carbons in eicosane flexibility contribu...

Yuhong Zhang

Papers

Constant pressure molecular dynamics simulation: The Langevin piston method

Computer simulation of liquid/liquid interfaces. I. Theory and application to octane/water

Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity

Computer simulation of liquid/liquid interfaces. II. Surface tension-area dependence of a bilayer and monolayer

Molecular Dynamics Simulations of Neat Alkanes: The Viscosity Dependence of Rotational Relaxation