Programme

I.1 -- Invited, VCTP-47

Date: Monday, 1 August 2022

Time: 08:40 - 09:20

COVID-19: Molecular dynamics simulations

Hoang Linh Nguyen (1,2,3), Nguyen Quoc Thai (1,4), Phuong H. Nguyen (5) and Mai Suan Li (6)

(1) Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam (2) Ho Chi Minh City University of Technology (HCMUT), Ho Chi Minh City 700000, Vietnam (3) Vietnam National University, Ho Chi Minh City 700000, Vietnam (4) Dong Thap University, 783 Pham Huu Lau Street, Ward 6, Cao Lanh City, Dong Thap, Vietnam (5) CNRS, Universit ́e de Paris, UPR9080, Laboratoire de Biochimie Th ́eorique, Paris,France ; Institut de Biologie Physico-Chimique, FondationEdmond de Rothschild, PSLResearch University, Paris, France (6) Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, 02-668, Warsaw, Poland

The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. To understand the binding mechanism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions.

Presenter: Nguyen Hoang Linh