DeepScaffold: A Comprehensive Tool for Scaffold-Based De Novo Drug Discovery Using Deep Learning.

ABSTRACT

The ultimate goal of drug design is to find novel compounds with desirable pharmacological properties. Designing molecules retaining particular scaffolds as their core structures is an efficient way to obtain potential drug candidates. We propose a scaffold-based molecular generative model for drug discovery, which performs molecule generation based on a wide spectrum of scaffold definitions, including Bemis-Murcko scaffolds, cyclic skeletons, and scaffolds with specifications on side-chain properties. The model can generalize the learned chemical rules of adding atoms and bonds to a given scaffold. The generated compounds were evaluated by molecular docking in DRD2 targets, and the results demonstrated that this approach can be effectively applied to solve several drug design problems, including the generation of compounds containing a given scaffold and de novo drug design of potential drug candidates with specific docking scores.