A team of researchers from Seoul National University in South Korea, University of Cambridge in the United Kingdom, and Lehigh University in Pennsylvania have worked together to produce the first open-source all-atom models of a full-length ‘spike’ or S protein, which enables SARS-CoV-2, the virus that causes covid-19, to enter host cells.
The model-building program is open access and can be found from the home page of Charmm-GUI, a program that simulates complex biomolecular systems simply, precisely, and quickly. Wonpil Im, PhD, the developer of Charmm-GUI, describes the program as a “computational microscope” that enables scientists to understand molecular-level interactions that cannot be observed any other way.
“Our models are the first fully-glycosylated full-length SARS-CoV-2 spike (S) protein models that are available to other scientists,” says Im. “I was fortunate to collaborate with Dr. Chaok Seok from Seoul National University in Korea and Dr. Tristan Croll from University of Cambridge in the UK. Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models.”
Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of COVID-19, according to Im.
The S protein structure was determined with cryo-EM with the RBD up, and with the RBD down. But this model has many missing residues. So, they first modeled the missing amino acid residues, and then other missing domains. In addition, they modeled all potential glycans (or carbohydrates) attached to the S protein. These glycans prevent antibody recognition, which makes it difficult to develop a vaccine. They also built a viral membrane system of an S protein for molecular dynamics simulation.
- Woo H, Park SJ, Choi YK, et al. Developing a fully-glycosylated full-length SARS-CoV-2 spike protein model in a viral membrane. J Phys Chem B. Epub. June 19, 2020; doi: 10.1021/acs.jpcb.0c04553.
A model of an S-protein. Illustration by Yeolkyo Choi, PhD/Lehigh University.