Integrative modeling of SARS-COV2 envelope structure

We request computational resources to model and study coarse-grained and all-atom structures of SARS-COV2 envelope that includes three structural proteins, S, M, and E, as well as lipid molecules. The ab-initio modeling of the envelope structure is challenging due to the lack of high-resolution CryoEM or CryoTM structures of not just a coronavirus, but any virus from the whole Nidovirales order. Furthermore, in spite of the progress of structural biology and bioinformatics, two of the three protein components of the envelope either have not been properly modeled (M dimer) or have been modeled with partially missing key parts (TM and HR2 domains of S trimer). By integrating experimentally extracted information about protein stoichiometries, local and global geometry of the envelope structure, and geometry of the assembly of constituting components, such as a grid-packing of M-dimer complexes, with homology-based and fragment based protein structure modeling as well as coarse-grain and all-atom molecular dynamics simulations, we propose to model and simulate the motions of the (1) individual protein complexes of S, M, and E proteins in the lipid bilayer, (2) local all-atomic envelope substructure involving a grid of M-dimers and several S trimer proteins, (3) a coarse-grain model of the envelope, and (4) all-atom model of the envelope. This project is an international collaboration that includes the research group of PI with expertise in structural bioinformatics and modeling large molecular assemblies, as well as two groups with complementary expertise: Prof. Benjamin Neumann group at Texas A&M University with expertise in electron microscopy of coronaviruses and Prof. Sewert-Jan Marrink group at U. of Groningem, Netherlands with expertise in molecular dynamics of large-scale molecular systems. Obtaining the structure of SARS-COV2 envelope will bring us one step closer to understanding molecular mechanisms behind COVID-19 infections and expedite the development of nano-particle based treatments that mimic the structural properties of the virion particles.