DeepCubist: Molecular Generator for Designing Peptidomimetics based on Complex three-dimensional scaffolds

Autor: Kohei, Umedera, Atsushi, Yoshimori, Hengwei, Chen, Hiroyuki, Kouji, Hiroyuki, Nakamura, Jürgen, Bajorath
Rok vydání: 2022
Předmět:
Zdroj: Journal of Computer-Aided Molecular Design. 37:107-115
ISSN: 1573-4951
0920-654X
Popis: 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.
Databáze: OpenAIRE
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