MSTP in PhD Training
Program: Computational and Systems Biology
Current advisor: Alex Holehouse, PhD
Undergraduate university: University of Sciences-Philadelphia, 2019
Enrollment year: 2019
Understanding the structural changes that lead to NSP16 activation by using DiffNets.
This past summer I worked in the lab of Dr. Gregory Bowman. I was involved in testing of an algorithm called DiffNets. DiffNets is a dimensionality reduction algorithm that learns important structural differences between protein variants and correlates them with activity of that protein variant. The testing was first done on a beta lactamase protein as there already was a model of how certain mutations lead to structural changes which lead to its activation. Next we used DiffNets on one of the non-structural proteins of SARS-CoV 2 called NSP16. NSP16 methylates Cap-0 to Cap-1 using SAM and is activated by NSP10. Cap-1 enhances translation and is important for immune system evasion. By using DiffNets on molecular dynamics simulations of NSP16 alone and in complex with NSP10, we wanted to learn what structural changes in the presence of NSP10 lead to NSP16 activation. This would allow for a more efficient prediction of how certain mutations would affect its function.
Vithani N, Ward MD, Zimmerman MI, Novak B, Borowsky JH, Singh S, Bowman GR. 2021 SARS-CoV2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential. Biophys J, ():S0006-3495(21)00254-X.