Tags

Type your tag names separated by a space and hit enter

Enhanced binding of the N501Y-mutated SARS-CoV-2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations.
FEBS Lett. 2021 May; 595(10):1454-1461.FL

Abstract

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (B.1.1.7 and B.1351) have emerged harbouring mutations that make them highly contagious. The N501Y mutation within the receptor-binding domain (RBD) of the spike protein of these SARS-CoV-2 variants may enhance binding to the human angiotensin-converting enzyme 2 (hACE2). However, no molecular explanation for such an enhanced affinity has so far been provided. Here, using all-atom molecular dynamics simulations, we show that Y501 in the mutated RBD can be well-coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, which may increase the overall binding affinity of the RBD for hACE2 by approximately 0.81 kcal·mol-1 . The binding dynamics revealed in our study may provide a working model to facilitate the design of more effective antibodies.

Authors+Show Affiliations

Computational Biological Center, IBM Thomas J. Watson Research, Yorktown Heights, New York, NY, USA.Neoland Biosciences, Medford, MA, USA.Computational Biological Center, IBM Thomas J. Watson Research, Yorktown Heights, New York, NY, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33728680

Citation

Luan, Binquan, et al. "Enhanced Binding of the N501Y-mutated SARS-CoV-2 Spike Protein to the Human ACE2 Receptor: Insights From Molecular Dynamics Simulations." FEBS Letters, vol. 595, no. 10, 2021, pp. 1454-1461.
Luan B, Wang H, Huynh T. Enhanced binding of the N501Y-mutated SARS-CoV-2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations. FEBS Lett. 2021;595(10):1454-1461.
Luan, B., Wang, H., & Huynh, T. (2021). Enhanced binding of the N501Y-mutated SARS-CoV-2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations. FEBS Letters, 595(10), 1454-1461. https://doi.org/10.1002/1873-3468.14076
Luan B, Wang H, Huynh T. Enhanced Binding of the N501Y-mutated SARS-CoV-2 Spike Protein to the Human ACE2 Receptor: Insights From Molecular Dynamics Simulations. FEBS Lett. 2021;595(10):1454-1461. PubMed PMID: 33728680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced binding of the N501Y-mutated SARS-CoV-2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations. AU - Luan,Binquan, AU - Wang,Haoran, AU - Huynh,Tien, Y1 - 2021/04/03/ PY - 2021/3/9/revised PY - 2021/2/5/received PY - 2021/3/10/accepted PY - 2021/3/18/pubmed PY - 2021/6/1/medline PY - 2021/3/17/entrez KW - ACE2 KW - N501Y KW - SARS-CoV-2 KW - antibody KW - spike protein SP - 1454 EP - 1461 JF - FEBS letters JO - FEBS Lett VL - 595 IS - 10 N2 - Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (B.1.1.7 and B.1351) have emerged harbouring mutations that make them highly contagious. The N501Y mutation within the receptor-binding domain (RBD) of the spike protein of these SARS-CoV-2 variants may enhance binding to the human angiotensin-converting enzyme 2 (hACE2). However, no molecular explanation for such an enhanced affinity has so far been provided. Here, using all-atom molecular dynamics simulations, we show that Y501 in the mutated RBD can be well-coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, which may increase the overall binding affinity of the RBD for hACE2 by approximately 0.81 kcal·mol-1 . The binding dynamics revealed in our study may provide a working model to facilitate the design of more effective antibodies. SN - 1873-3468 UR - https://www.unboundmedicine.com/medline/citation/33728680/Enhanced_binding_of_the_N501Y_mutated_SARS_CoV_2_spike_protein_to_the_human_ACE2_receptor:_insights_from_molecular_dynamics_simulations_ DB - PRIME DP - Unbound Medicine ER -