Docking and Biomolecular Simulations on Computer Grids: Status and Trends

Tantar, Alexandru-Adrian; Conilleau, Sebastien; Parent, Benjamin; Melab, Nouredine; Brillet, Lorraine; Roy, Sylvaine; Talbi, El‐Ghazali; Horvath, Dragos

doi:10.2174/157340908785747438

Cited by 17 publications

(16 citation statements)

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“…In the predicted structure, the H1-S2 loop (residues 35–60) locked the oryzalin-binding site, preventing molecules from penetrating inside. An early version of the conformational sampling tool S4MPLE [ 20 ] specifically operating on the torsional degrees of freedom only [ 21 ] was used to explore alternative putative poses of that loop. Main chains and side chains of the loop aminoacids, as well as side chains of residues putatively in contact with loop residues were declared mobile, while freezing the rest of the protein to its initial geometry.…”

Section: Resultsmentioning

confidence: 99%

Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

Soleilhac

Brillet-Guéguen

Roussel

et al. 2018

IJMS

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Dinitroanilines are chemical compounds with high selectivity for plant cell α-tubulin in which they promote microtubule depolymerization. They target α-tubulin regions that have diverged over evolution and show no effect on non-photosynthetic eukaryotes. Hence, they have been used as herbicides over decades. Interestingly, dinitroanilines proved active on microtubules of eukaryotes deriving from photosynthetic ancestors such as Toxoplasma gondii and Plasmodium falciparum, which are responsible for toxoplasmosis and malaria, respectively. By combining differential in silico screening of virtual chemical libraries on Arabidopsis thaliana and mammal tubulin structural models together with cell-based screening of chemical libraries, we have identified dinitroaniline related and non-related compounds. They inhibit plant, but not mammalian tubulin assembly in vitro, and accordingly arrest A. thaliana development. In addition, these compounds exhibit a moderate cytotoxic activity towards T. gondii and P. falciparum. These results highlight the potential of novel herbicidal scaffolds in the design of urgently needed anti-parasitic drugs.

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Section: Resultsmentioning

confidence: 99%

Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

Soleilhac

Brillet-Guéguen

Roussel

et al. 2018

IJMS

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“…Tantar et al [39] give an overview of current efforts how large scale parallel computing is applied to molecular simulations. The authors are also involved in the Docking@Grid project [40] that aims to define the optimal deployment architecture for Grid based molecular docking simulations, and provide the accurate definition of the molecular energy surface.…”

Section: Related Workmentioning

confidence: 99%

Parameter Sweep Workflows for Modelling Carbohydrate Recognition

et al. 2010

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Carbohydrate recognition is a phenomenon critical to a number of biological functions in humans. Understanding the dynamic behaviour of oligosaccharides should help in the discovery of the mechanisms which lead to specific and selective recognition of carbohydrates by proteins. Computer programs which can provide insight into such biological recognition processes have significant potential to contribute to biomedical research if the results of the simulation can prove consistent with the outcome of conventional wet laboratory experiments. In order to validate these simulation tools and support their wider uptake by the bio-scientist research community, high-level easy to use integrated environments are required to run massively parallel simulation workflows. This paper describes how the ProSim Science Gateway, based on the WS-PGRADE Grid portal, has been created to execute and visualise the results of complex parameter sweep workflows for modelling carbohydrate recognition.T. Kiss (B) · G. Terstyanszky · N. Weingarten

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“…The procedure is similar to that used by other workers. 15,[52][53][54][55][56][57][58][59] We took advantage of the InfiniBand (InfiniBand Trade Association, Beaverton, OR) capabilities of the Grid5000 clusters providing 100% Transfert_100 Transfert_200 Transfert_300 Transfert_400 Transfert_500 Transfert_600 Transfert_700 Transfert_800 Transfert_900 Transfert_1000 Transfert_1100 Transfert_1200 Transfert_1300 Transfert_1400 Transfert_1500 Transfert_1600 Transfert_1700 Transfert_1800 Transfert_1900 Transfert_2000 Transfert_2100 Local_100 Transfert_100 Transfert_200 Transfert_300 Transfert_400 Transfert_500 Transfert_600 Transfert_700 Transfert_800 Transfert_900 Transfert_1000 Transfert_1100 Transfert_1200 Transfert_1300 Transfert_1400 Transfert_1500 Transfert_1600 Transfert_1700 Transfert_1800 Transfert_1900 Transfert_2000 Transfert_2100 high throughput virtual screening on cluster grid Dovepress submit your manuscript | www.dovepress.com Dovepress efficiency for each node on which NAMD was running. The results of these calculations are shown in Table 1.…”

Section: Namd Final Refinementsmentioning

confidence: 99%

Efficiency of a hierarchical protocol for high throughput structure-based virtual screening on GRID5000 cluster grid

Ghemtio¹,

Jeannot²,

Maigret³

2010

OAB

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Most modern computational techniques in the drug discovery areas put demands on large computer resources. Grid computing offers a powerful alternative way of running computationally intensive applications. One field of the drug innovation process that can benefit greatly from the use of grid resources is the high-throughput virtual screening approach for docking huge chemical compound libraries into known protein-binding sites. The use of computational grids is the combination of computer resources from multiple administrative domains, heterogeneous, and geographically dispersed applications to a common task that requires a great number of computer-processing cycles or the need to process large amounts of data. This study detailed a screening campaign, on Grid5000 cluster grid computing infrastructure, concerning the ZINC database, from which a subset of ∼600,000 "drug-like" molecules was extracted, against three structures of the liver-X receptor β (LXR β). A funnel strategy was used for that purpose, starting from a fast but simple shape matching procedure and achieved with more complex molecular dynamics simulations. From a total of ∼91 million three-dimensional conformations which were generated at the beginning of the funnel and after intermediate filtering steps, the process ended with 45 putative hits. The GRID5000 is a highly reconfigurable, controllable, and monitorable experimental cluster grid, connecting nine sites geographically distributed in France, and featuring more than 3,200 processors and 5,700 cores. To hide the complexity of the grid system from the user, the GRID5000 has been used through the virtual screening manager for grid computing (VSM-G) platform, dedicated to in silico screening and to provide maximum computing power by using grid resources efficiently. The whole screening process required around 82 days (78 days of pre-processing and 3.6 days for the docking funnel itself) and utilized 3,144 nodes over nine sites. The use of grid infrastructures and hierarchical filtering protocol enable us to perform evaluations of the binding capabilities of millions of compounds on several conformations of a given target and propose that, with a low cost, most promising compounds for in vitro tests.

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Docking and Biomolecular Simulations on Computer Grids: Status and Trends

Cited by 17 publications

References 0 publications

Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

Parameter Sweep Workflows for Modelling Carbohydrate Recognition

Efficiency of a hierarchical protocol for high throughput structure-based virtual screening on GRID5000 cluster grid

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