Ensemble-based simulation and analysis workflow for design of novel peptidic inhibitors of COVID-19 main protease

The proposal aims to generate preliminary data that can be experimentally verified in the design of novel peptide inhibitors of the COVID-19 main protease (PDB 6LU7) using a workflow we previously designed for designing potential inhibitors of Ebola membrane fusion via a NSF RAPID award and a 2M node hour allocation on Blue Waters. The automated workflow does design with Rosetta based on a known peptide scaffold, optimizes the structures with microsecond-scale MD simulations with GPU-optimized AMBER, and analysis with CPPTRAJ and MM-PBSA methods. The team has considerable HPC experience on NSF funded machines from XSEDE, Blue Waters, and currently Frontera and the workflow is already running (with the exception of Rosetta on IBM machines where it does not compile). The intent is to get some lead compounds quickly that can be tested experimentally in the lab of Professor Schmidt in my department which would serve as the preliminary data for a joint experimental/theoretical proposal by the Cheatham and Schmidt labs.