Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Thursday Speaker Abstracts

INTRODUCING THE AUTOMATED LIGAND SEARCHER (ALISE) Luise Jacobsen 1 ; Peter J Husen 1 ; Thomas Teusch 2 ; Ilia A Solov’yov 2 ; 1 University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Odense M, Denmark 2 Carl von Ossietzky University of Oldenburg, Department of Physics, Oldenburg, Germany The elaborate and automated drug discovery tool, the Automated Ligand Searcher (ALISE), is introduced. ALISE applies a three-stage workflow with each stage applying an increasingly sophisticated computational method: molecular docking, molecular dynamics simulations, and free energy perturbation simulations, respectively, to approximate the binding free energy of ligands binding to a receptor. Poorly performing ligands are gradually segregated to narrow down the number of potential ligands. Two exemplary case studies of ALISE focusing on the polymerase basic protein 2 in influenza A virus and the main protease of SARS-CoV-2 as drug targets demonstrated that each of ALISE's three stages provides increasingly refined and valuable information on assessing the energetics between the drug candidates and a receptor. Ultimately, the automation and comprehensiveness of ALISE make it a valuable tool for improved and faster drug development workflows.

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