Computational Advances in Structural Biology

Abstract:

The main target for vaccine development is the SARS-CoV-2 spike protein (S), which facilitates the viral entry into host cells. Using cryo-electron tomography in combination with subtomogram averaging (STA) it is possible to examine the structure of S in its natural environment, as well as measure its distribution and abundance on viral surfaces. Our data demonstrates that S has a high degree of flexibility, which is enabled by three hinges on its stalk. This unexpected orientational freedom can cause problems for any analysis that is based on averaging. Combining molecular dynamics simulations with contextual STA-based analysis helps us to partially overcome this issue and gain better understanding of the previously unknown structure of the stalk.