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Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design

The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to gen...

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Detalles Bibliográficos
Autores principales: Gil L., Alejandro, Valiente, Pedro A., Pascutti, Pedro G., Pons, Tirso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134243/
https://www.ncbi.nlm.nih.gov/pubmed/21760810
http://dx.doi.org/10.1155/2011/657483
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author Gil L., Alejandro
Valiente, Pedro A.
Pascutti, Pedro G.
Pons, Tirso
author_facet Gil L., Alejandro
Valiente, Pedro A.
Pascutti, Pedro G.
Pons, Tirso
author_sort Gil L., Alejandro
collection PubMed
description The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to generate inhibitor libraries for these enzymes, and together with computational methodologies have been demonstrated capable for the selection of lead compounds. The high structural flexibility of plasmepsins, revealed by their X-ray structures and molecular dynamics simulations, made even more complicated the prediction of putative binding modes, and therefore, the use of common computational tools, like docking and free-energy calculations. In this review, we revised the computational strategies utilized so far, for the structure-function relationship studies concerning the plasmepsin family, with special focus on the recent advances in the improvement of the linear interaction estimation (LIE) method, which is one of the most successful methodologies in the evaluation of plasmepsin-inhibitor binding affinity.
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spelling pubmed-31342432011-07-14 Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design Gil L., Alejandro Valiente, Pedro A. Pascutti, Pedro G. Pons, Tirso J Trop Med Review Article The development of efficient and selective antimalariais remains a challenge for the pharmaceutical industry. The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs. Combinatorial synthesis is currently being used to generate inhibitor libraries for these enzymes, and together with computational methodologies have been demonstrated capable for the selection of lead compounds. The high structural flexibility of plasmepsins, revealed by their X-ray structures and molecular dynamics simulations, made even more complicated the prediction of putative binding modes, and therefore, the use of common computational tools, like docking and free-energy calculations. In this review, we revised the computational strategies utilized so far, for the structure-function relationship studies concerning the plasmepsin family, with special focus on the recent advances in the improvement of the linear interaction estimation (LIE) method, which is one of the most successful methodologies in the evaluation of plasmepsin-inhibitor binding affinity. Hindawi Publishing Corporation 2011 2011-07-03 /pmc/articles/PMC3134243/ /pubmed/21760810 http://dx.doi.org/10.1155/2011/657483 Text en Copyright © 2011 Alejandro Gil L. et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Gil L., Alejandro
Valiente, Pedro A.
Pascutti, Pedro G.
Pons, Tirso
Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title_full Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title_fullStr Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title_full_unstemmed Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title_short Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design
title_sort computational perspectives into plasmepsins structure—function relationship: implications to inhibitors design
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134243/
https://www.ncbi.nlm.nih.gov/pubmed/21760810
http://dx.doi.org/10.1155/2011/657483
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