In this project, we will resolve the role of covalently attached oligosaccharides in the conformational transition of the SARS-CoV-2 S protein from a closed, non-infectious state to an open one that can bind to its receptor ACE2 on human cells. The oligosaccharides form a so-called “glycan shield”, which comprises 20% of the mass of the system and contributes to immune system evasion. We will use highly scalable replica-exchange umbrella sampling to map a two-dimensional free-energy landscape of the conformational change in non- and fully-glycosylated states. The large scale of the calculation requires supercomputing at the petascale level as provided by Summit. Furthermore, intermediate states along the opening pathway for the native, glycosylated S protein will be used in an ongoing high-throughput virtual screening effort at ORNL.
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