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Journal of Tropical Medicine
Volume 2011, Article ID 657483, 15 pages
Review Article

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

1Laboratorio de Biología Computacional y Diseño de Proteínas, Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, Cuba
2Instituto de Biofísica Carlos Chagas Filho, Universidad Federal do Rio de Janeiro, Brazil

Received 1 February 2011; Revised 1 May 2011; Accepted 3 May 2011

Academic Editor: Gerd Pluschke

Copyright © 2011 Alejandro Gil L. et al. 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.


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.