title: Computer-aided drug design of novel PLA2 inhibitor candidates for treatment of snakebite.
abstract: 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.
authors.affiliation: Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto-SP, Brazil.
authors.forename: Lorane Izabel da S
authors.initials: LI
authors.lastname: Hage-Melim
authors.forename: Carlos Henrique  T de P
authors.initials: CH
authors.lastname: da Silva
authors.forename: Evandro P
authors.initials: EP
authors.lastname: Semighini
authors.forename: Carlton A
authors.initials: CA
authors.lastname: Taft
authors.forename: Suely V
authors.initials: SV
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D064801:Phospholipase A2 Inhibitors; D011487:Protein Conformation; D012909:Snake Bites / Q000188:drug therapy*; D012984:Software
chemical_list: D003435:Crotalid Venoms; D064801:Phospholipase A2 Inhibitors; C078097:bothropstoxin