DeepCubist: Molecular Generator for Designing Peptidomimetics based on Complex three-dimensional scaffolds.
J Comput Aided Mol Des
; 37(2): 107-115, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36462089
ABSTRACT
Mimicking bioactive conformations of peptide segments involved in the formation of protein-protein interfaces with small molecules is thought to represent a promising strategy for the design of protein-protein interaction (PPI) inhibitors. For compound design, the use of three-dimensional (3D) scaffolds rich in sp3-centers makes it possible to precisely mimic bioactive peptide conformations. Herein, we introduce DeepCubist, a molecular generator for designing peptidomimetics based on 3D scaffolds. Firstly, enumerated 3D scaffolds are superposed on a target peptide conformation to identify a preferred template structure for designing peptidomimetics. Secondly, heteroatoms and unsaturated bonds are introduced into the template via a deep generative model to produce candidate compounds. DeepCubist was applied to design peptidomimetics of exemplary peptide turn, helix, and loop structures in pharmaceutical targets engaging in PPIs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Peptidomiméticos
Idioma:
En
Revista:
J Comput Aided Mol Des
Asunto de la revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón