| 1. |
- Abraham, Mark James, et al.
(författare)
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Sharing Data from Molecular Simulations
- 2019
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Ingår i: Journal of Chemical Information and Modeling. - : AMER CHEMICAL SOC. - 1549-9596 .- 1549-960X. ; 59:10, s. 4093-4099
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Tidskriftsartikel (refereegranskat)abstract
- Given the need for modern researchers to produce open, reproducible scientific output, the lack of standards and best practices for sharing data and workflows used to produce and analyze molecular dynamics (MD) simulations has become an important issue in the field. There are now multiple well-established packages to perform molecular dynamics simulations, often highly tuned for exploiting specific classes of hardware, each with strong communities surrounding them, but with very limited interoperability/transferability options. Thus, the choice of the software package often dictates the workflow for both simulation production and analysis. The level of detail in documenting the workflows and analysis code varies greatly in published work, hindering reproducibility of the reported results and the ability for other researchers to build on these studies. An increasing number of researchers are motivated to make their data available, but many challenges remain in order to effectively share and reuse simulation data. To discuss these and other issues related to best practices in the field in general, we organized a workshop in November 2018 (https://bioexcel.eu/events/workshop-on-sharing-data-from-molecular-simulations/). Here, we present a brief overview of this workshop and topics discussed. We hope this effort will spark further conversation in the MD community to pave the way toward more open, interoperable, and reproducible outputs coming from research studies using MD simulations.
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| 2. |
- Apostolov, Rossen, et al.
(författare)
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Membrane attachment facilitates ligand access to the active site in monoamine oxidase A
- 2009
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 48:25, s. 5864-5873
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Tidskriftsartikel (refereegranskat)abstract
- Monoamine oxidase membrane enzymes are responsible for the catalytic breakdown of extra- and intracellular neurotransmitters and are targets for the development of central nervous system drugs. We analyzed the dynamics of rat MAOA by performing multiple independent molecular dynamics simulations of membrane-bound and membrane-free forms to clarify the relationship between the mechanics of the enzyme and its function, with particular emphasis on the significance of membrane attachment. Principal component analysis of the simulation trajectories as well as correlations in the fluctuations of the residues pointed to the existence of three domains that define the global dynamics of the protein. Interdomain anticorrelated movements in the membrane-bound system facilitated the relaxation of interactions between residues surrounding the substrate cavity and induced conformational changes which expanded the active site cavity and opened putative pathways for substrate uptake and product release. Such events were less pronounced in the membrane-free system due to differences in the nature of the dominant modes of motion. The presence of the lipid environment is suggested to assist in decoupling the interdomain motions, consistent with the observed reduction in enzyme activity under membrane-free conditions. Our results are also in accordance with mutational analysis which shows that modifications of interdomain hinge residues decrease the activity of rat MAOA in solution.
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| 3. |
- Apostolov, Rossen, et al.
(författare)
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Scalable Software Services for Life Science
- 2011
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Ingår i: Proceedings of 9th HealthGrid conference.
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Konferensbidrag (refereegranskat)abstract
- Life Science is developing into one of the largest e- Infrastructure users in Europe, in part due to the ever-growing amount of biological data. Modern drug design typically includes both sequence bioinformatics, in silico virtual screening, and free energy calculations, e.g. of drug binding. This development will accelerate tremendously, and puts high demands on simulation software and support services. e-Infrastructure projects such as PRACE/DEISA have made important advances on hardware and scalability, but have largely been focused on theoretical scalability for large systems, while typical life science applications rather concern small-to-medium size molecules. Here, we propose to address this with by implementing new techniques for efficient small-system parallelization combined with throughput and ensemble computing to enable the life science community to exploit the largest next-generation e-Infrastructures. We will also build a new cross-disciplinary Competence Network for all of life science, to position Europe as the world-leading community for development and maintenance of this software e-Infrastructure. Specifically, we will (1) develop new hierarchical parallelization approaches explicitly based on ensemble and high-throughput computing for new multi-core and streaming/GPU architectures, and establish open software standards for data storage and exchange, (2) implement, document, and maintain such techniques in pilot European open-source codes such as the widely used GROMACS & DALTON, a new application for ensemble simulation (DISCRETE), and large-scale bioinformatics protein annotation, (3) create a Competence Centre for scalable life science software to strengthen Europe as a major software provider and to enable the community to exploit e-Infrastructures to their full extent. This Competence Network will provide training and support infrastructure, and establish a long-term framework for maintenance and optimization of life science codes.
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| 4. |
- Kikugawa, Gota, et al.
(författare)
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Application of MDGRAPE-3, a Special Purpose Board for Molecular Dynamics Simulations, to Periodic Biomolecular Systems
- 2009
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 30:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- We describe the application of a special purpose board for molecular dynamics simulations, named MDGRAPE-3, to the problem of simulating periodic bio-molecular systems. MDGRAPE-3 is the latest board in a series of hardware accelerators designed to calculate the nonbonding long-range interactions much more rapidly than normal processors. So far, MDGRAPEs were mainly applied to isolated systems, where very many nonbonded interactions were calculated without any distance cutoff. However, in order to regulate the density and pressure during simulations of membrane embedded protein systems, one has to evaluate interactions under periodic boundary conditions. For this purpose, we implemented the Particle-Mesh Ewald (PME) method, and its approximation with distance cutoffs and charge neutrality as proposed by Wolf et al., using MDGRAPE-3. When the two methods were applied to simulations of two periodic biomolecular systems, a single MDGRAPE-3 achieved 30-40 times faster computation times than a single conventional processor did in the both cases. Both methods are shown to have the same molecular structures and dynamics of the systems.
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| 5. |
- Kutzner, C., et al.
(författare)
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Scaling of the GROMACS 4.6 molecular dynamics code on SuperMUC
- 2014
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Ingår i: Advances in Parallel Computing. - 0927-5452 .- 1879-808X. ; 25, s. 722-727
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Tidskriftsartikel (refereegranskat)abstract
- Here we report on the performance of GROMACS 4.6 on the SuperMUC cluster at the Leibniz Rechenzentrum in Garching. We carried out benchmarks with three biomolecular systems consisting of eighty thousand to twelve million atoms in a strong scaling test each. The twelve million atom simulation system reached a performance of 49 nanoseconds per day on 32,768 cores.
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| 6. |
- Lundborg, Magnus, et al.
(författare)
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An Efficient and Extensible Format, Library, and API for Binary Trajectory Data from Molecular Simulations
- 2014
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 35:3, s. 260-269
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Tidskriftsartikel (refereegranskat)abstract
- Molecular dynamics simulations is an important application in theoretical chemistry, and with the large high-performance computing resources available today the programs also generate huge amounts of output data. In particular in life sciences, with complex biomolecules such as proteins, simulation projects regularly deal with several terabytes of data. Apart from the need for more cost-efficient storage, it is increasingly important to be able to archive data, secure the integrity against disk or file transfer errors, to provide rapid access, and facilitate exchange of data through open interfaces. There is already a whole range of different formats used, but few if any of them (including our previous ones) fulfill all these goals. To address these shortcomings, we present Trajectory Next Generation (TNG)a flexible but highly optimized and efficient file format designed with interoperability in mind. TNG both provides state-of-the-art multiframe compression as well as a container framework that will make it possible to extend it with new compression algorithms without modifications in programs using it. TNG will be the new file format in the next major release of the GROMACS package, but it has been implemented as a separate library and API with liberal licensing to enable wide adoption both in academic and commercial codes.
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| 7. |
- Natarajan Arul, Murugan, et al.
(författare)
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Association dynamics and linear and nonlinear optical properties of an N-acetylaladanamide probe in a POPC membrane
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:36, s. 13590-13597
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Tidskriftsartikel (refereegranskat)abstract
- Along with the growing evidence that relates membrane abnormalities to various diseases, biological membranes have been acknowledged as targets for therapy. Any such abnormality in the membrane structure alters the membrane potential which in principle can be captured by measuring properties of specific optical probes. There exists by now many molecular probes with absorption and fluorescence properties that are sensitive to local membrane structure and to the membrane potential. To suggest new high-performance optical probes for membrane-potential imaging it is important to understand in detail the membrane-induced structural changes in the probe, the membrane association dynamics of the probe, and its membrane-specific optical properties. To contribute to this effort, we here study an optical probe, N-acetylaladanamide (NAAA), in the presence of a POPC lipid bilayer using a multiscale integrated approach to assess the probe structure, dynamics, and optical properties in its membrane-bound status and in water solvent. We find that the probe eventually assimilates into the membrane with a specific orientation where the hydrophobic part of the probe is buried inside the lipid bilayer, while the hydrophilic part is exposed to the water solvent. The computed absorption maximum is red-shifted when compared to the gas phase. The computations of the two-photon absorption and second harmonic generation cross sections of the NAAA probe in its membrane-bound state which is of its first kind in the literature suggest that this probe can be used for imaging the membrane potential using nonlinear optical microscopy.
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| 8. |
- Paulsen, Peter Aasted, et al.
(författare)
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The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology
- 2013
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Ingår i: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 30:2, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- The Na,K-ATPase is essential to all animals, since it maintains the electrochemical gradients that energize the plasma membrane. Naturally occurring inhibitors of the pump from plants have been used pharmaceutically in cardiac treatment for centuries. The inhibitors block the pump by binding on its extracellular side and thereby locking it. To explore the possibilities for designing an alternative way of targeting the pump function, we have examined the structural requirements for binding to a pocket that accommodates the two C-terminal residues, YY, in the crystal structures of the pump. To cover the sample space of two residues, we first performed docking studies with the 400 possible dipeptides. For validation of the in silico predictions, pumps with 13 dipeptide sequences replacing the C-terminal YY were expressed in Xenopus laevis oocytes and examined with electrophysiology. Our data show a significant correlation between the docking scores from two different methods and the experimentally determined sodium affinities, which strengthens the previous hypothesis that sodium binding is coupled to docking of the C-terminus. From the dipeptides that dock the best and better than wild-type YY, it may therefore be possible to develop specific drugs targeting a previously unexplored binding pocket in the sodium pump.
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| 9. |
- Pronk, Sander, et al.
(författare)
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GROMACS 4.5 : a high-throughput and highly parallel open source molecular simulation toolkit
- 2013
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 29:7, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations.
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| 10. |
- Tsourtou, Flora D., et al.
(författare)
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Molecular Dynamics Simulation of Amorphous Poly(3-hexylthiophene)
- 2020
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 53:18, s. 7810-7824
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Tidskriftsartikel (refereegranskat)abstract
- Molecular dynamics (MD) simulations are employed to study the effect of chain length and temperature on the density and conformational properties of regioregular poly(3-hexylthiophene), also denoted as RR-P3HT, in its pure amorphous phase. First, several widely used all-atom force fields (FFs) currently available in the literature are evaluated by comparing their predictions for the density, mean-square chain end-to-end distance, mean-square chain radius-of-gyration, and persistence length of RR-P3HT oligomers at temperatures above their melting point with the limited available experimental data in the literature. Then, with one of the most promising from these FFs, we extend the MD simulations to higher-chain-length P3HT systems (containing up to 150 monomers per chain) at various temperatures. The MD results indicate that the density and persistence length of amorphous P3HT increase slightly with chain length approaching limiting asymptotic values equal to 0.788 +/- 0.003 g cm(-3) and 21 +/- 0.4 angstrom, respectively, at temperature T = 700 K and pressure P = 1 atm. This is attributed to excess chain end free volume effects that are significant at low molecular weights. On the contrary, the effective conjugation length, which is found to become larger than the persistence length only above a certain molecular weight, shows a stronger dependence on chain length. Both of these characteristic lengths are found to increase with decreasing temperature due to the increasing relative population of planar (cis and trans) conformational states of the inter-ring torsion angle. The probability distribution of the maximum length of conjugated segments along a P3HT chain coincides with the theoretical distribution of a longest run of "heads" in a coin-flip experiment. Our MD results suggest that short-chain-length RR-P3HT chains in their bulk amorphous phase are semiflexible but, as their molecular weight increases, they adopt more and more random coil conformations, especially at higher temperatures.
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