Programme

P.59 -- Poster, VCTP-47

Date: Thursday, 4 August 2022

Time: 08:30 - 10:00

SARS-CoV-2 Omicron Variant Binds to Human Cells More Strongly than the Wild Type: Evidence from Molecular Dynamics Simulation.

Hoang Linh Nguyen (1), Nguyen Quoc Thai (2), Phuong H Nguyen(3), Mai Suan Li (4)

(1) Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City 700000, Vietnam; (2) Dong Thap University, 783 Pham Huu Lau Street, Ward 6, Cao Lanh City, Dong Thap 8100, Vietnam; (3) CNRS, Universit́e de Paris, UPR9080, Laboratoire de Biochimie Th́eorique, Paris, France; Institut de Biologie Physico-Chimique, FondationEdmond de Rothschild, PSL Research University, Paris 75006, France; (4) Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, Warsaw 02-668, Poland

The emergence of the variant of concern Omicron (B.1.1.529) of the severe acute respiratory syndrome coronavirus 2 has aggravated the Covid-19 pandemic due to its very contagious ability. The high infection rate may be due to the high binding affinity of Omicron to human cells, but both experimental and computational studies have yielded conflicting results on this issue. Some studies have shown that the Omicron variant binds to human angiotensin-converting enzyme 2 (hACE2) more strongly than the wild type (WT), but other studies have reported comparable binding affinities. To shed light on this open problem, in this work, we calculated the binding free energy of the receptor binding domain (RBD) of the WT and Omicron spike protein to hACE2 using all-atom molecular dynamics simulation and the molecular mechanics Poisson–Boltzmann surface area method. We showed that Omicron binds to human cells more strongly than the WT due to increased RBD charge, which enhances electrostatic interaction with negatively charged hACE2. N440K, T478K, E484A, Q493R, and Q498R mutations in the RBD have been found to play a critical role in the stability of the RBD-hACE2 complex. The effect of homogeneous and heterogeneous models of glycans coating the viral RBD and the peptidyl domain of hACE2 was examined. Although the total binding free energy is not sensitive to the glycan model, the distribution of per-residue interaction energies depends on it. In addition, glycans have a little effect on the binding affinity of the WT RBD to hACE2.

Presenter: Nguyen Quoc Thai