Discovery of RTA ricin subunit inhibitors: a computational study using PM7 quantum chemical method and steered molecular dynamics.
J Biomol Struct Dyn
; 40(12): 5427-5445, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-33526002
ABSTRACT
Ricin is a potent toxin derived from the castor bean plant and comprises two subunits, RTA and RTB. Because of its cytotoxicity, ricin has alarmed world authorities for its potential use as a chemical weapon. Ricin also affects castor bean agribusiness, given the risk of animal and human poisoning. Over the years, many groups attempted to propose small-molecules that bind to the RTA active site, the catalytic chain. Despite such efforts, there is still no effective countermeasure against ricin poisoning. The computational study carried out in the present work renews the discussion about small-molecules that may inhibit this toxin. Here, a structure-based virtual screening protocol capable of discerning active RTA inhibitors from inactive ones was performed to screen over 2 million compounds from the ZINC database to find novel scaffolds that strongly bind into the active site of the RTA. Besides, a novel score method based on ligand undocking force profiles and semi-empirical quantum chemical calculations provided insights into the rescore of docking poses. Summing up, the filtering steps pointed out seven main compounds, with the SCF00-451 as a promising candidate to inhibit the killing activity of such potent phytotoxin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ricina
/
Toxinas Biológicas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil