Force field validation for nucleic acid simulations: comparing energies and dynamics of a DNA dodecamer

Important questions exist regarding the quality of force fields used in molecular dynamics (MD) simulations and their interoperable use with other available MD implementations. NAMD is one of the most efficient and scalable parallel molecular dynamics codes for large-scale biomolecular simulations in the open source domain. It is the aim of this article to analyze and compare the dynamics of a benchmark DNA dodecamer d(CTTTTGCAAAAG)2 system, including its binding to a specific drug molecule arising from the use of various simulation protocols in NAMD using Amber98, with the dynamics arising from simulations of the same dodecamer using Amber98 in the AMBER package, one of the most well-established simulation codes for nucleic acids. Based upon a set of validation benchmarks, the details of which are discussed, we find that nucleic acid simulations using NAMD give meaningful results and that the essential features of the resulting dynamics are similar to those arising from the AMBER package. This sets the stage for reliable large-scale simulations of nucleic acids using NAMD.     

Lightweight object oriented structure analysis: Tools for building tools to analyze molecular dynamics simulations

LOOS (Lightweight Object Oriented Structure‐analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool‐writer. In addition, LOOS is bundled with over 140 prebuilt tools, including suites of tools for analyzing simulation convergence, three‐dimensional histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only four core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development. © 2014 Wiley Periodicals, Inc.     

IBIsCO: a molecular dynamics simulation package for coarse-grained simulation

IBIsCO is a parallel molecular dynamics simulation package developed specially for coarse-grained simulations with numerical potentials derived by the iterative Boltzmann inversion (IBI) method (Reith et al., J Comput Chem 2003, 24, 1624). In addition to common features of molecular dynamics programs, the techniques of dissipative particle dynamics (Groot and Warren, J Chem Phys 1997, 107, 4423) and Lowe-Andersen dynamics (Lowe, Europhys Lett 1999, 47, 145) are implemented, which can be used both as thermostats and as sources of friction to compensate the loss of degrees of freedom by coarse-graining. The reverse nonequilibrium molecular dynamics simulation method (Müller-Plathe, Phys Rev E 1999, 59, 4894) for the calculation of viscosities is also implemented. Details of the algorithms, functionalities, implementation, user interfaces, and file formats are described. The code is parallelized using PE_MPI on PowerPC architecture. The execution time scales satisfactorily with the number of processors.     

Complex molecular assemblies at hand via interactive simulations

Studying complex molecular assemblies interactively is becoming an increasingly appealing approach to molecular modeling. Here we focus on interactive molecular dynamics (IMD) as a textbook example for interactive simulation methods. Such simulations can be useful in exploring and generating hypotheses about the structural and mechanical aspects of biomolecular interactions. For the first time, we carry out low‐resolution coarse‐grain IMD simulations. Such simplified modeling methods currently appear to be more suitable for interactive experiments and represent a well‐balanced compromise between an important gain in computational speed versus a moderate loss in modeling accuracy compared to higher resolution all‐atom simulations. This is particularly useful for initial exploration and hypothesis development for rare molecular interaction events. We evaluate which applications are currently feasible using molecular assemblies from 1900 to over 300,000 particles. Three biochemical systems are discussed: the guanylate kinase (GK) enzyme, the outer membrane protease T and the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors complex involved in membrane fusion. We induce large conformational changes, carry out interactive docking experiments, probe lipid–protein interactions and are able to sense the mechanical properties of a molecular model. Furthermore, such interactive simulations facilitate exploration of modeling parameters for method improvement. For the purpose of these simulations, we have developed a freely available software library called MDDriver. It uses the IMD protocol from NAMD and facilitates the implementation and application of interactive simulations. With MDDriver it becomes very easy to render any particle‐based molecular simulation engine interactive. Here we use its implementation in the Gromacs software as an example. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

A parallel molecular dynamics strategy

This article presents a strategy to perform molecular dynamics simulations using parallel processing techniques on a parallel-distributed loosely coupled system consisting of IBM host computers (4341 and 4381) with attached scientific processors (FPS-164). This substantially enhances our ability to perform fast and more realistic large scale many-body trajectory simulations. A powerful extention of the computational range of molecular dynamics the parallel approach offers the opportunity to substantially reduce the simulation time to allow a longer simulation period to study more realistic models and larger systems. It is flexible and uses, for the most part, standard products and straightforward implementation with a broad range of applicability. The implementation of a simulation of water molecules with the inclusion of two- and three-body interactions is discussed. Some considerations in the design and implementation of parallel programs on a loosely coupled system are also presented.     

Scalable fine-grained parallelization of plane-wave-based ab initio molecular dynamics for large supercomputers

Many systems of great importance in material science, chemistry, solid-state physics, and biophysics require forces generated from an electronic structure calculation, as opposed to an empirically derived force law to describe their properties adequately. The use of such forces as input to Newton's equations of motion forms the basis of the ab initio molecular dynamics method, which is able to treat the dynamics of chemical bond-breaking and -forming events. However, a very large number of electronic structure calculations must be performed to compute an ab initio molecular dynamics trajectory, making the efficiency as well as the accuracy of the electronic structure representation critical issues. One efficient and accurate electronic structure method is the generalized gradient approximation to the Kohn-Sham density functional theory implemented using a plane-wave basis set and atomic pseudopotentials. The marriage of the gradient-corrected density functional approach with molecular dynamics, as pioneered by Car and Parrinello (R. Car and M. Parrinello, Phys Rev Lett 1985, 55, 2471), has been demonstrated to be capable of elucidating the atomic scale structure and dynamics underlying many complex systems at finite temperature. However, despite the relative efficiency of this approach, it has not been possible to obtain parallel scaling of the technique beyond several hundred processors on moderately sized systems using standard approaches. Consequently, the time scales that can be accessed and the degree of phase space sampling are severely limited. To take advantage of next generation computer platforms with thousands of processors such as IBM's BlueGene, a novel scalable parallelization strategy for Car-Parrinello molecular dynamics is developed using the concept of processor virtualization as embodied by the Charm++ parallel programming system. Charm++ allows the diverse elements of a Car-Parrinello molecular dynamics calculation to be interleaved with low latency such that unprecedented scaling is achieved. As a benchmark, a system of 32 water molecules, a common system size employed in the study of the aqueous solvation and chemistry of small molecules, is shown to scale on more than 1500 processors, which is impossible to achieve using standard approaches. This degree of parallel scaling is expected to open new opportunities for scientific inquiry.     

The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections

There is considerable interest in developing methodologies for the accurate evaluation of free energies, especially in the context of biomolecular simulations. Here, we report on a reexamination of the recently developed metadynamics method, which is explicitly designed to probe "rare events" and areas of phase space that are typically difficult to access with a molecular dynamics simulation. Specifically, we show that the accuracy of the free energy landscape calculated with the metadynamics method may be considerably improved when combined with umbrella sampling techniques. As test cases, we have studied the folding free energy landscape of two prototypical peptides: Ace-(Gly)(2)-Pro-(Gly)(3)-Nme in vacuo and trialanine solvated by both implicit and explicit water. The method has been implemented in the classical biomolecular code AMBER and is to be distributed in the next scheduled release of the code.