Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Thursday Speaker Abstracts

NOVEL MODELING TOOLS AND SIMULATION APPROACHES FOR EXASCALE STRUCTURAL BIOLOGY Emad Tajkhorshid ; 1 University of Illinois, Biochemistry, Urbana, IL, USA The viral pandemic and its huge impact on all societal aspects of human life, and in particular the power of vaccination in its control, continue to remind us of the key importance of molecular research in handling major health conditions facing humanity. Tremendous advances have been achieved in molecular and structural biological research of the SARS-CoV2 viral components presenting potential drug targets against the infection, as well as in obtaining structural information on the entire viral particle (e.g., through cryoEM studies). In parallel, a major objective in computational studies has been the development of complete models for the viral components and particle, at various desired resolutions, with the goal of completing the step needed for simulating the behavior of the whole virus in different media, and modeling its interaction, fusion, and penetration into the host cell. Such models could also provide details on the interaction of biologics such as antibodies with the virus, as well as a structural framework to develop novel strategies against the virus. Modeling such large molecular assemblies as the viral particle at a sufficiently high quality for detailed simulation and structural studies, however, poses major challenges. In this talk, I will share our latest efforts in developing a robust protocol to assemble a very large number of lipids (100,000s) and proteins (10,000s) into viral envelopes robust and stable for simulation studies. The protocol employs several advanced modeling techniques, interleaved with simulations at different resolutions, to construct optimally packed arrangements of lipids and proteins at any desired densities. In addition to spherical membranes representing viral envelopes, the protocol can be used to construct lipid-protein molecular assemblies of any shape. Along with lessons learnt and solutions to challenges during the process, I will also discuss the results of the simulations performed on whole viral envelope structures.

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