The high arithmetic performance and intrinsic parallelism of recent graphical processing units (GPUs) can offer a technological edge for molecular dynamics simulations. ACEMD is a production-class ...biomolecular dynamics (MD) engine supporting CHARMM and AMBER force fields. Designed specifically for GPUs it is able to achieve supercomputing scale performance of 40 ns/day for all-atom protein systems with over 23 000 atoms. We provide a validation and performance evaluation of the code and run a microsecond-long trajectory for an all-atom molecular system in explicit TIP3P water on a single workstation computer equipped with just 3 GPUs. We believe that microsecond time scale molecular dynamics on cost-effective hardware will have important methodological and scientific implications.
High-throughput molecular dynamics (MD) simulations are a computational method consisting of using multiple short trajectories, instead of few long ones, to cover slow biological time scales. ...Compared to long trajectories this method offers the possibility to start the simulations in successive batches, building a knowledgeable model of the available data to inform subsequent new simulations iteratively. Here, we demonstrate an automatic, iterative, on-the-fly method for learning and sampling molecular simulations in the context of ligand binding for the case of trypsin–benzamidine binding. The method uses Markov state models to learn a simplified model of the simulations and decide where best to sample from, achieving a converged binding affinity in approximately one microsecond, 1 order of magnitude faster than classical sampling. This method demonstrates for the first time the potential of adaptive sampling schemes in the case of ligand binding.
An important step in structure-based drug design consists in the prediction of druggable binding sites. Several algorithms for detecting binding cavities, those likely to bind to a small drug ...compound, have been developed over the years by clever exploitation of geometric, chemical and evolutionary features of the protein.
Here we present a novel knowledge-based approach that uses state-of-the-art convolutional neural networks, where the algorithm is learned by examples. In total, 7622 proteins from the scPDB database of binding sites have been evaluated using both a distance and a volumetric overlap approach. Our machine-learning based method demonstrates superior performance to two other competitive algorithmic strategies.
DeepSite is freely available at www.playmolecule.org. Users can submit either a PDB ID or PDB file for pocket detection to our NVIDIA GPU-equipped servers through a WebGL graphical interface.
gianni.defabritiis@upf.edu.
Supplementary data are available at Bioinformatics online.
Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has ...transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features.
The smooth particle mesh Ewald summation method is widely used to efficiently compute long-range electrostatic force terms in molecular dynamics simulations, and there has been considerable work in ...developing optimized implementations for a variety of parallel computer architectures. We describe an implementation for Nvidia graphical processing units (GPUs) which are general purpose computing devices with a high degree of intrinsic parallelism and arithmetic performance. We find that, for typical biomolecular simulations (e.g., DHFR, 26K atoms), a single GPU equipped workstation is able to provide sufficient performance to permit simulation rates of ≈50 ns/day when used in conjunction with the ACEMD molecular dynamics package and exhibits an accuracy comparable to that of a reference double-precision CPU implementation.
We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing ...service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.
Although molecular dynamics simulation methods are useful in the modeling of macromolecular systems, they remain computationally expensive, with production work requiring costly high-performance ...computing (HPC) resources. We review recent innovations in accelerating molecular dynamics on graphics processing units (GPUs), and we describe GPUGRID, a volunteer computing project that uses the GPU resources of nondedicated desktop and workstation computers. In particular, we demonstrate the capability of simulating thousands of all-atom molecular trajectories generated at an average of 20 ns/day each (for systems of ∼30 000−80 000 atoms). In conjunction with a potential of mean force (PMF) protocol for computing binding free energies, we demonstrate the use of GPUGRID in the computation of accurate binding affinities of the Src SH2 domain/pYEEI ligand complex by reconstructing the PMF over 373 umbrella sampling windows of 55 ns each (20.5 μs of total data). We obtain a standard free energy of binding of −8.7 ± 0.4 kcal/mol within 0.7 kcal/mol from experimental results. This infrastructure will provide the basis for a robust system for high-throughput accurate binding affinity prediction.
The use of modern, high-performance graphical processing units (GPUs) for acceleration of scientific computation has been widely reported. The majority of this work has used the CUDA programming ...model supported exclusively by GPUs manufactured by NVIDIA. An industry standardisation effort has recently produced the OpenCL specification for GPU programming. This offers the benefits of hardware-independence and reduced dependence on proprietary tool-chains. Here we describe a source-to-source translation tool, “Swan” for facilitating the conversion of an existing CUDA code to use the OpenCL model, as a means to aid programmers experienced with CUDA in evaluating OpenCL and alternative hardware. While the performance of equivalent OpenCL and CUDA code on fixed hardware should be comparable, we find that a real-world CUDA application ported to OpenCL exhibits an overall 50% increase in runtime, a reduction in performance attributable to the immaturity of contemporary compilers. The ported application is shown to have platform independence, running on both NVIDIA and AMD GPUs without modification. We conclude that OpenCL is a viable platform for developing portable GPU applications but that the more mature CUDA tools continue to provide best performance.
Program title: Swan
Catalogue identifier: AEIH_v1_0
Program summary URL:
http://cpc.cs.qub.ac.uk/summaries/AEIH_v1_0.html
Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland
Licensing provisions: GNU Public License version 2
No. of lines in distributed program, including test data, etc.: 17 736
No. of bytes in distributed program, including test data, etc.: 131 177
Distribution format: tar.gz
Programming language: C
Computer: PC
Operating system: Linux
RAM: 256 Mbytes
Classification: 6.5
External routines: NVIDIA CUDA, OpenCL
Nature of problem: Graphical Processing Units (GPUs) from NVIDIA are preferentially programed with the proprietary CUDA programming toolkit. An alternative programming model promoted as an industry standard, OpenCL, provides similar capabilities to CUDA and is also supported on non-NVIDIA hardware (including multicore ×86 CPUs, AMD GPUs and IBM Cell processors). The adaptation of a program from CUDA to OpenCL is relatively straightforward but laborious. The
Swan tool facilitates this conversion.
Solution method:
Swan performs a translation of CUDA kernel source code into an OpenCL equivalent. It also generates the C source code for entry point functions, simplifying kernel invocation from the host program. A concise host-side API abstracts the CUDA and OpenCL APIs. A program adapted to use
Swan has no dependency on the CUDA compiler for the host-side program. The converted program may be built for either CUDA or OpenCL, with the selection made at compile time.
Restrictions: No support for CUDA C++ features
Running time: Nominal
The separation between molecular and mesoscopic length and time scales poses a severe limit to molecular simulations of mesoscale phenomena. We describe a hybrid multiscale computational technique ...which addresses this problem by keeping the full molecular nature of the system where it is of interest and coarse graining it elsewhere. This is made possible by coupling molecular dynamics with a mesoscopic description of realistic liquids based on Landau's fluctuating hydrodynamics. We show that our scheme correctly couples hydrodynamics and that fluctuations, at both the molecular and continuum levels, are thermodynamically consistent. Hybrid simulations of sound waves in bulk water and reflected by a lipid monolayer are presented as illustrations of the scheme.
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