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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doaj-275bd33f8fce4c5d9991953a594a8a782020-11-24T23:56:01ZengHindawi LimitedJournal of Tropical Medicine1687-96861687-96942011-01-01201110.1155/2011/657483657483Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors DesignAlejandro Gil L.0Pedro A. Valiente1Pedro G. Pascutti2Tirso Pons3Laboratorio de Biología Computacional y Diseño de Proteínas, Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, CubaLaboratorio de Biología Computacional y Diseño de Proteínas, Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, CubaInstituto de Biofísica Carlos Chagas Filho, Universidad Federal do Rio de Janeiro, BrazilLaboratorio de Biología Computacional y Diseño de Proteínas, Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, CubaThe 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.http://dx.doi.org/10.1155/2011/657483 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alejandro Gil L. Pedro A. Valiente Pedro G. Pascutti Tirso Pons |
spellingShingle |
Alejandro Gil L. Pedro A. Valiente Pedro G. Pascutti Tirso Pons Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design Journal of Tropical Medicine |
author_facet |
Alejandro Gil L. Pedro A. Valiente Pedro G. Pascutti Tirso Pons |
author_sort |
Alejandro Gil L. |
title |
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_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_sort |
computational perspectives into plasmepsins structure—function relationship: implications to inhibitors design |
publisher |
Hindawi Limited |
series |
Journal of Tropical Medicine |
issn |
1687-9686 1687-9694 |
publishDate |
2011-01-01 |
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. |
url |
http://dx.doi.org/10.1155/2011/657483 |
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1725460045713375232 |