Comparison of the binding characteristics of SARS-CoV and SARS-CoV-2 RBDs to ACE2 at different temperatures by MD simulations

Abstract Temperature plays a significant role in the survival and transmission of SARS-CoV (severe acute respiratory syndrome coronavirus) and SARS-CoV-2. To reveal the binding differences of SARS-CoV and SARS-CoV-2 receptor-binding domains (RBDs) to angiotensin-converting enzyme 2 (ACE2) at differe...

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Vydáno v:Briefings in bioinformatics Ročník 22; číslo 2; s. 1122 - 1136
Hlavní autoři: Yan, Fang-Fang, Gao, Feng
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Oxford University Press 22.03.2021
Oxford Publishing Limited (England)
Témata:
ACE2
Amino Acid Sequence
Angiotensin
Angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - chemistry
Angiotensin-Converting Enzyme 2 - metabolism
Binding
Cluster Analysis
Coronaviruses
COVID-19
Differential thermal analysis
Electrostatic properties
Humans
Infectious diseases
Molecular dynamics
Molecular Dynamics Simulation
Peptidyl-dipeptidase A
Principal Component Analysis
Problem Solving Protocol
Protein Binding
Recombination hot spots
Residues
SARS-CoV-2 - metabolism
Sequence Homology, Amino Acid
Severe acute respiratory syndrome coronavirus 2
Temperature
COVID-19
SARS-CoV-2
hierarchical clustering analysis
principle component analysis
molecular dynamics simulation
ISSN:1467-5463, 1477-4054, 1477-4054
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Shrnutí:Abstract Temperature plays a significant role in the survival and transmission of SARS-CoV (severe acute respiratory syndrome coronavirus) and SARS-CoV-2. To reveal the binding differences of SARS-CoV and SARS-CoV-2 receptor-binding domains (RBDs) to angiotensin-converting enzyme 2 (ACE2) at different temperatures at atomic level, 20 molecular dynamics simulations were carried out for SARS-CoV and SARS-CoV-2 RBD–ACE2 complexes at five selected temperatures, i.e. 200, 250, 273, 300 and 350 K. The analyses on structural flexibility and conformational distribution indicated that the structure of the SARS-CoV-2 RBD was more stable than that of the SARS-CoV RBD at all investigated temperatures. Then, molecular mechanics Poisson–Boltzmann surface area and solvated interaction energy approaches were combined to estimate the differences in binding affinity of SARS-CoV and SARS-CoV-2 RBDs to ACE2; it is found that the binding ability of ACE2 to the SARS-CoV-2 RBD was stronger than that to the SARS-CoV RBD at five temperatures, and the main reason for promoting such binding differences is electrostatic and polar interactions between RBDs and ACE2. Finally, the hotspot residues facilitating the binding of SARS-CoV and SARS-CoV-2 RBDs to ACE2, the key differential residues contributing to the difference in binding and the interaction mechanism of differential residues that exist at all investigated temperatures were analyzed and compared in depth. The current work would provide a molecular basis for better understanding of the high infectiousness of SARS-CoV-2 and offer better theoretical guidance for the design of inhibitors targeting infectious diseases caused by SARS-CoV-2.
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ISSN:1467-5463
1477-4054
1477-4054
DOI:10.1093/bib/bbab044