Network analysis uncovers the communication structure of SARS-CoV-2 spike protein identifying sites for immunogen design
Pedro D. Manrique,
Srirupa Chakraborty,
Rory Henderson,
Robert J. Edwards,
Rachael Mansbach,
Kien Nguyen,
Victoria Stalls,
Carrie Saunders,
Katayoun Mansouri,
Priyamvada Acharya,
Bette Korber,
S. Gnanakaran
Affiliations
Pedro D. Manrique
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Srirupa Chakraborty
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Rory Henderson
Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University, Durham, NC 27710, USA
Robert J. Edwards
Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University, Durham, NC 27710, USA
Summary: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand the structure and dynamics of this complex pathogen. The spike glycoprotein of SARS-CoV-2 is a significant target for immunogens as it is the means by which the virus enters human cells, while simultaneously sporting mutations responsible for immune escape. These functional and escape processes are regulated by complex molecular-level interactions. Our study presents quantitative insights on domain and residue contributions to allosteric communication, immune evasion, and local- and global-level control of functions through the derivation of a weighted graph representation from all-atom MD simulations. Focusing on the ancestral form and the D614G-variant, we provide evidence of the utility of our approach by guiding the selection of a mutation that alters the spike’s stability. Taken together, the network approach serves as a valuable tool to evaluate communication “hot-spots” in proteins to guide design of stable immunogens.
