Advances and Challenges in De Novo Drug Design Using Three-Dimensional Deep Generative Models

Abstract

A persistent goal for de novo drug design is to generate novel chemical compounds with desirable properties in a labor-, time-, and cost-efficient manner. Deep generative models provide alternative routes to this goal. Numerous model architectures and optimization strategies have been explored in recent years, most of which have been developed to generate two-dimensional molecular structures. Some generative models aiming at three-dimensional (3D) molecule generation have also been proposed, gaining attention for their unique advantages and potential to directly design drug-like molecules in a target-conditioning manner. This review highlights current developments in 3D molecular generative models combined with deep learning and discusses future directions for de novo drug design.