WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures
Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic...
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ftdoajarticles:oai:doaj.org/article:79dafc38ad264de3b4d7b96f132b4b42 2023-05-15T15:16:16+02:00 WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures Kenyon Colin Maass Astrid Kim Doman Isea Raul Degliesposti Gianluca Dacosta Ana Botha Marli Salzemann Jean Kasam Vinod Rastelli Giulio Hofmann-Apitius Martin Breton Vincent 2009-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-88 https://doaj.org/article/79dafc38ad264de3b4d7b96f132b4b42 EN eng BMC http://www.malariajournal.com/content/8/1/88 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-88 1475-2875 https://doaj.org/article/79dafc38ad264de3b4d7b96f132b4b42 Malaria Journal, Vol 8, Iss 1, p 88 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-88 2022-12-31T13:51:04Z Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR), and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software on computational grids in finding hits against three different ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Kenyon Colin Maass Astrid Kim Doman Isea Raul Degliesposti Gianluca Dacosta Ana Botha Marli Salzemann Jean Kasam Vinod Rastelli Giulio Hofmann-Apitius Martin Breton Vincent WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR), and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software on computational grids in finding hits against three different ... |
format |
Article in Journal/Newspaper |
author |
Kenyon Colin Maass Astrid Kim Doman Isea Raul Degliesposti Gianluca Dacosta Ana Botha Marli Salzemann Jean Kasam Vinod Rastelli Giulio Hofmann-Apitius Martin Breton Vincent |
author_facet |
Kenyon Colin Maass Astrid Kim Doman Isea Raul Degliesposti Gianluca Dacosta Ana Botha Marli Salzemann Jean Kasam Vinod Rastelli Giulio Hofmann-Apitius Martin Breton Vincent |
author_sort |
Kenyon Colin |
title |
WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
title_short |
WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
title_full |
WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
title_fullStr |
WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
title_full_unstemmed |
WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures |
title_sort |
wisdom-ii: screening against multiple targets implicated in malaria using computational grid infrastructures |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-88 https://doaj.org/article/79dafc38ad264de3b4d7b96f132b4b42 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 88 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/88 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-88 1475-2875 https://doaj.org/article/79dafc38ad264de3b4d7b96f132b4b42 |
op_doi |
https://doi.org/10.1186/1475-2875-8-88 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
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1766346564522999808 |