GENERA: A Combined Genetic/Deep-Learning Algorithm for Multiobjective Target-Oriented De Novo Design.
J Chem Inf Model
; 63(16): 5107-5119, 2023 08 28.
Article
em En
| MEDLINE
| ID: mdl-37556857
ABSTRACT
This study introduces a new de novo design algorithm called GENERA that combines the capabilities of a deep-learning algorithm for automated drug-like analogue design, called DeLA-Drug, with a genetic algorithm for generating molecules with desired target-oriented properties. Specifically, GENERA was applied to the angiotensin-converting enzyme 2 (ACE2) target, which is implicated in many pathological conditions, including COVID-19. The ability of GENERA to de novo design promising candidates for a specific target was assessed using two docking programs, PLANTS and GLIDE. A fitness function based on the Pareto dominance resulting from computed PLANTS and GLIDE scores was applied to demonstrate the algorithm's ability to perform multiobjective optimizations effectively. GENERA can quickly generate focused libraries that produce better scores compared to a starting set of known ACE-2 binders. This study is the first to utilize a DL-based algorithm designed for analogue generation as a mutational operator within a GA framework, representing an innovative approach to target-oriented de novo design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aprendizado Profundo
/
COVID-19
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália