"Several Birds with One Stone": Exploring the Potential of AI Methods for Multi-Target Drug Design

Abstract Background: Drug discovery is a time-consuming and expensive process. Artificial intelligence (AI) methodologies have been adopted to cut costs and speed up the drug development process, serving as promising in silico approaches to efficiently design novel drug candidates targeting various health conditions. Most existing AI-driven drug discovery studies follow a single-target approach which focuses on identifying compounds that bind a single target (i.e., one-drug-one-target approach). Polypharmacology is a relatively new concept that takes a systematic approach to search for a compound (or a combination of compounds) that can bind two or more carefully selected protein biomarkers simultaneously to synergistically treat the disease. Recent studies have demonstrated that multi-target drugs offer superior therapeutic potentials compared to single-target drugs. However, it is intuitively thought that searching for multi-target drugs is more challenging than finding single-target drugs. At present, it is unclear how AI approaches perform in designing multi-target drugs. Results: In this paper, we comprehensively investigated the performance of multi-objective AI approaches for multi-target drug design. Conclusion: Our findings are quite counterintuitive demonstrating that, in fact, AI approaches for multi-target drug design are able to efficiently generate more high-quality novel compounds than the single-target approaches while satisfying a number of constraints.