Exploring the effects of N234 and N343 linked glycans to SARS CoV 2 spike protein pocket accessibility using Gaussian accelerated molecular dynamics simulations.

The N234 and N343-linked glycans of the SARS-CoV 2 spike protein are known to stabilize the up-conformation of its receptor-binding domains (RBDs), enabling human angiotensin enzyme 2 (hACE2) receptor binding. However, the effect of spike-hACE2 binding on these important glycans remains poorly understood, and these changes could have implications in the development of drugs that inhibit viral entry. In this study, Gaussian accelerated molecular dynamics (GaMD) simulations of the hACE2-free and hACE2-bound spike protein are performed.

Complementary Pocket and Network-Based Approach to Search for Spike Protein Allosteric Pocket Sites.

COVID-19 is a persistent public health concern due to the emergence of more virulent and contagious variants resulting from mutations in the spike protein. The spike protein in newer variants, including Delta and Omicron, may be less sensitive to neutralizing antibodies and have a more favorable binding environment to the human ACE2 receptor. In the interest of identifying anti-COVID-19 allosteric drugs, a network-based approach based on coarse-grained molecular dynamics (CGMD) simulations, in complement to pocket-based analysis, is used to identify the possible allosteric pathways of the wild-type, Delta, and Omicron BA.