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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2011
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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. |
format | Online Article Text |
id | pubmed-3134243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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