computational perspectives into plasmepsins structure—function relationship implications to inhibitors design计算结构功能主义视角为plasmepsins影响抑制剂设计的关系.pdfVIP

Hindawi Publishing Corporation Journal of Tropical Medicine Volume 2011, Article ID 657483, 15 pages doi:10.1155/2011/657483 Review Article Computational Perspectives into Plasmepsins Structure—Function Relationship: Implications to Inhibitors Design Alejandro Gil L.,1 Pedro A. Valiente,1 Pedro G. Pascutti,2 and Tirso Pons1 1 Laboratorio de Biologıa Computacional y Diseno de Proteınas, Centro de Estudio de Proteınas (CEP), ´ ˜ ´ ´ Facultad de Biologıa, Universidad de La Habana, Cuba ´ 2 Instituto de Biofısica Carlos Chagas Filho, Universidad Federal do Rio de Janeiro, Brazil ´ Correspondence should be addressed to Tirso Pons, tirsopons@ 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