Navigating Chemical Space by Interfacing Generative Artificial Intelligence and Molecular Docking.

Journal: Journal of chemical information and modeling
Published Date:

Abstract

Here, we report the implementation and application of a simple, structure-aware framework to generate target-specific screening libraries. Our approach combines advances in generative artificial intelligence (AI) with conventional molecular docking to explore chemical space on the unique physicochemical properties of the active site of a biomolecular target. As a demonstration, we used our framework, which we refer to as sample-and-dock, to construct focused libraries for cyclin-dependent kinase type-2 (CDK2) and the active site of the main protease (M) of the SARS-CoV-2 virus. We envision that the sample-and-dock framework could be used to generate theoretical maps of the chemical space specific to a given target and so provide information about its molecular recognition characteristics.

Authors

  • Ziqiao Xu
    Chemistry Department, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
  • Orrette R Wauchope
    Department of Natural Sciences, City University of New York, Baruch College, New York, New York 10010, United States.
  • Aaron T Frank
    Biophysics Program, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.