Oak Ridge National Laboratory is managed by UT-Battelle LLC for the US Department of Energy
Dynamic Structural models
Proteins from the SARS-CoV-2 Proteome
To facilitate structure-based identification of drugs that target SARS-CoV-2 proteins, we are performing temperature replica-exchange molecular dynamics (T-REMD) simulations with GROMACS of viral proteins and providing representative snapshots from RMSD-based clustering. These MD snapshots are available for commercial and non-commercial use and are primarily intended for use in ensemble docking studies, which we are performing on the Summit supercomputer at ORNL.
Details of the simulations will be added in the near future, but the main protocol is outlined in the following preprint:
Smith MD and Smith JC, Repurposing therapeutics for COVID-19: Supercomputer-based docking to the viral spike protein and viral spike protein-human ACE2 interface. ChemRxiv, 2020.
Nsp3 (ADP ribose phosphatase domain)
We used the 1.5 angstrom X-ray co-crystal structure of the protein (PDB entry: 6w02, DOI: 10.2210/pdb6W02/pdb) and removed ADP ribose prior to performing the MD simulations.
Nsp5 Proteinase 3CL-PRO (main protease)
Cleaves the C-terminus of the replicase polyprotein at multiple sites. We used the 1.75 Angstrom X-ray crystal structure with a small-molecule ligand bound (PDB entry: 6y2e. DOI: 10.2210/pdb6Y2E/pdb).
Spike glycoprotein (receptor binding domain)
The spike glycoprotein initiates infection by binding to human ACE2 and potentially other targets. We used the 3.08 angstrom X-ray co-crystal structure of the RBD bound to an antibody (PDB entry: 6w41, DOI: 10.2210/pdb6W41/pdb). The antibody was removed prior to performing the MD simulations.