Modeling virus actions & inhibition
The motions of the spike proteins, and viral entry into the cell. Simmerling and R. Amaro (UCSD) are starting from the cryo-EM structure (Zhang, Science 2020), adding missing details and loops with Coutsias, using Brikard. They perform MD and pathway computations to explore the protein’s motions and conformational changes. They aim to see how the spike protein Receptor Binding Domain (RBD) binds to the cell’s ACE2 receptor.
The native structures of SARS-CoV-2 proteins. The structures are not yet known for most of the 29 viral proteins. Roy Nassar in the Dill group is using MELD x MD on the amino-acid sequences, plus MELD targetting protocols, to compute the native structures of 19 small SARS-CoV-2 proteins.
Binding poses & affinities of potential inhibitors. Kozakov, Rizzo, and Brini & Liu in the Dill group seek small-molecules to inhibit of the virus. One effort is on the viral Main Protease, a protein that is essential for viral maturation. They start with fast rigid-body screens, then refine them at atomistic detail using MELD x MD. Another effort explores other novel inhibition strategies. P. Tonge at Stony Brook University is doing companion experiments.