Research: HIV, Ebola, Corona, and other similar viruses are at constant warfare with the human immune system. While the viruses evolve to come up with unique strategies to overcome the immune system, our body must keep up and counteract the threat. One critical battlefront in this war is the glycan (sugar) coating on the viral envelope proteins that act as a shield from antibodies. Understanding the conformational topology of this sugar layer is of particular importance in order to guide vaccine design. However, experimental studies of the glycan barrier remain extremely challenging due to their structurally heterogeneous and dynamic nature. We have designed a set of computational tools to characterize this glycan shield and identify regions of vulnerability and resilience that can be harnessed towards vaccine design. There are four parts to this toolset: (i) high-throughput modeling pipeline to build a physiological ensemble of the glycoprotein in atomistic detail; (ii) describe global and local properties of the shield topology using graph theory; and (iii) quantify the shielding effect towards pinpointing regions which can act as antibody epitope; (iv) develop coarse-grained parameters for glycans in order to capture long temporal dynamics. In my talk, I will briefly go over these tools, describe how such methodology has been extensively validated using experimental cryo-electron microscopy, and how these can be used to guide immunogen design efforts. In the end, I will discuss the extension of these methods to other densely glycosylated systems, aiding in better understanding of the role of glycans in biological processes, as well as utilizing them for bio-inspired material design.
 

Biography: Srirupa Chakraborty obtained a PhD in Biophysics from the State University of New York at Buffalo in 2016, prior to which she had earned a B.S. in Physics from Presidency College, University of Calcutta, followed by M.S. in Physics from the Indian Institute of Technology – Guwahati (India). After a brief stint as a visiting scientist at IBM Watson Research Center where her research on cognitive learning platform design led to two patents, she has been a postdoctoral researcher at Los Alamos National Laboratory. There, her work developing novel tools and techniques to bridge in silico results and experimental data through theoretical modeling was recognized with the Wiley Computers in Chemistry Outstanding Research Award by the American Chemical Society in 2020, and an award by the Consortia for HIV/AIDS Vaccine Development (CHAVD) in 2019. Her research focus is in the interface of biology, chemistry and physics, where she uses computer-aided structural modeling and simulations of biomolecules. Her current research aims to elucidate the conformational dynamics of viral envelope glycoproteins and other densely glycosylated systems, ultimately designing knowledge-based therapeutic strategies and novel biomaterials.