Design of SARS-CoV-2 Main Protease Inhibitors Using Artificial Intelligence and Molecular Dynamic Simulations
Lars Elend, Luise Jacobsen, Tim Cofala, Jonas Prellberg, Thomas Teusch, Oliver Kramer, Ilia A. Solov'yov
Drug design is a time-consuming and cumbersome process due to the vast search spaceof drug-like molecules and the difficulty of investigating atomic and electronic interactions. Thepresent paper proposes a computational drug design workflow that combines artificial intelligence(AI) methods, i.e., an evolutionary algorithm and artificial neural network model, and molecular dynamics (MD) simulations to design and evaluate potential drug candidates. For the purpose of illustration, the proposed workflow was applied to design drug candidates against the main protease of severe acute respiratory syndrome coronavirus 2. From the ~140,000 molecules designed using AI methods, MD analysis identified two molecules as potential drug candidates.