Recent advances from computer-aided drug design to artificial intelligence drug design

Abstract

Computer-aided drug design (CADD), a cornerstone of modern drug discovery, can predict how a molecular structure relates to its activity and interacts with its target using structure-based and ligand-based methods. Fueled by ever-increasing data availability and continuous model optimization, artificial intelligence drug design (AIDD), as an enhanced iteration of CADD, has thrived in the past decade. AIDD demonstrates unprecedented opportunities in protein folding, property prediction, and molecular generation. It can also facilitate target identification, high-throughput screening (HTS), and synthetic route prediction. With AIDD involved, the process of drug discovery is greatly accelerated. Notably, AIDD offers the potential to explore uncharted territories of chemical space beyond current knowledge. In this perspective, we began by briefly outlining the main workflows and components of CADD. Then through showcasing exemplary cases driven by AIDD in recent years, we describe the evolving role of artificial intelligence (AI) in drug discovery from three distinct stages, that is, chemical library screening, linker generation, and de novo molecular generation. In this process, we attempted to draw comparisons between the features of CADD and AIDD.