Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

Multi-and many-objective optimization: present and future in de novo drug design

de novo Drug Design (dnDD) aims to create new molecules that satisfy multiple conflicting objectives. Since several desired properties can be considered in the optimization process, dnDD is naturally categorized as a many-objective optimization problem (ManyOOP), where more than three objectives must be simultaneously optimized. However, a large number of objectives typically pose several challenges that affect the choice and the design of optimization methodologies. Herein, we cover the application of multi- and many-objective optimization methods, particularly those based on Evolutionary Computation and Machine Learning techniques, to enlighten their potential application in dnDD. Additionally, we comprehensively analyze how molecular properties used in the optimization process are applied as either objectives or constraints to the problem. Finally, we discuss future research in many-objective optimization for dnDD, highlighting two important possible impacts: i) its integration with the development of multi-target approaches to accelerate the discovery of innovative and more efficacious drug therapies and ii) its role as a catalyst for new developments in more fundamental and general methodological frameworks in the field