Effect of mutation on structure, function and dynamics of receptor binding domain of human SARS-CoV-2 with host cell receptor ACE2: a molecular dynamics simulations study.

Journal of Biomolecular Structure & Dynamics
Budheswar DehuryMrutyunjay Suar

Abstract

Recent studies have pointed the role of angiotensin-converting enzyme-II (ACE2) in mediating the entry of SARS-CoV-2 to the host cell by binding to the receptor-binding domain (RBD) of viral spike protein, and successive priming by cellular proteases initiates the infection. SARS-CoV replication rate and disease severity is controlled by the binding affinity of RBD with ACE2. To understand, how mutations in the conserved residues of RBD affect the molecular interaction with ACE2, we generated five alanine mutants i.e. Y449A, N487A, Y489A, N501A and Y505A in the receptor binding motif (RBM) of the ACE2-RBD SARS-CoV-2 complex (PDB: 6M0J). Computational site directed mutagenesis induced dynamics in wild-type and mutant complexes were extensively studied through all-atoms molecular dynamics (MD) simulations of 150 ns. In silico mutational analysis revealed loss of important intermolecular hydrogen bonds and other non-bonded contacts, critical for molecular recognition of SARS-CoV-2 RBD to ACE2, which is well supported by saturation mutagenesis study of binding interface residues. MD simulations results showed that RBM motif is flexible, where mutant residues are relatively more mobile than corresponding wild-type residues. Global m...Continue Reading

References

Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
May 14, 1999·Current Opinion in Structural Biology·A Kitao, N Go
Aug 29, 2002·Nature Structural Biology·Martin Karplus, J Andrew McCammon
Oct 20, 2004·Hypertension·Matthew J HuentelmanDavid A Ostrov
Jun 28, 2005·Computational Biology and Chemistry·Yuan ZhangYang Zhong
May 27, 2010·Nucleic Acids Research·M L HekkelmanG Vriend
Feb 1, 2012·The Journal of Biological Chemistry·Kailang WuFang Li
Sep 26, 2013·Methods in Molecular Biology·Charles C David, Donald J Jacobs
Apr 29, 2016·PLoS Computational Biology·Tatiana MaximovaAmarda Shehu
Sep 1, 2016·Annual Review of Virology·Fang Li
Nov 8, 2016·Nature Methods·Jing HuangAlexander D MacKerell
Sep 22, 2018·Neuron·Scott A Hollingsworth, Ron O Dror
Feb 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Albert C PanDavid E Shaw
May 23, 2019·Nucleic Acids Research·Carlos H M RodriguesDavid B Ascher
Jan 26, 2020·Journal of Medical Virology·Geng LiJianguo Wu
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Apr 25, 2020·Nature Medicine·Waradon SungnakUNKNOWN HCA Lung Biological Network
Apr 27, 2020·The Science of the Total Environment·Hongchao QiZhijie Zhang
May 16, 2020·Biochemical and Biophysical Research Communications·Houcemeddine OthmanScott Hazelhurst
Aug 25, 2020·The Lancet. Microbe·Alex W H ChinLeo L M Poon

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Citations

May 13, 2021·The Journal of Physical Chemistry. B·Elhan TakaMert Gur
Jan 15, 2021·Immunological Medicine·Norma Saad, Salim Moussa
Jul 6, 2021·Physical Chemistry Chemical Physics : PCCP·Vincent BinetteNormand Mousseau
Aug 13, 2021·Journal of Chemical Theory and Computation·Arzu Uyar, Alex Dickson
Sep 15, 2021·Briefings in Bioinformatics·Wenyang ZhouQinghua Jiang

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BETA
PCA

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Grace
BIOVIA Discovery Studio Visualizer
VMD
gmx hbond
PyMOL
PRODIGY
PyMOL Molecular Graphics System
gmx do _ dssp
GROMOS
BIOVIA DSV

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