Computer-aided drug design of novel PLA2 inhibitor candidates for treatment of snakebite.
J Biomol Struct Dyn
; 27(1): 27-36, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19492860
Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine as active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction based on homology modeling. In addition, we have performed virtual screening in a large database yielding a set of potential bioactive inhibitors. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. We have performed molecular interaction fields (MIFs) calculations with the phospholipase model. Results confirm the important role of Lys49 for binding ligands and suggest three additional residues as well. We have proposed a theoretically nontoxic, drug-like, and potential novel BthTX-I inhibitor. These calculations have been used to guide the design of novel phospholipase inhibitors as potential lead compounds that may be optimized for future treatment of snakebite victims as well as other human diseases in which PLA(2) enzymes are involved.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mordeduras de Serpientes
/
Diseño de Fármacos
/
Venenos de Crotálidos
/
Inhibidores de Fosfolipasa A2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2009
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Reino Unido