Computational design of protein-based inhibitors of Plasmodium vivax subtilisin-like 1 protease.

ABSTRACT:

Background

Malaria remains a major global health concern. The development of novel therapeutic strategies is critical to overcome the selection of multiresistant parasites. The subtilisin-like protease (SUB1) involved in the egress of daughter Plasmodium parasites from infected erythrocytes and in their subsequent invasion into fresh erythrocytes has emerged as an interesting new drug target.

Findings

Using a computational approach based on homology modeling, protein-protein docking and mutation scoring, we designed protein-based inhibitors of Plasmodium vivax SUB1 (PvSUB1) and experimentally evaluated their inhibitory activity. The small peptidic trypsin inhibitor EETI-II was used as scaffold. We mutated residues at specific positions (P4 and P1) and calculated the change i

SUBMITTER: Bastianelli G 

PROVIDER: S-EPMC4208747 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature