Coevolution, Dynamics and Allostery Conspire in Shaping Cooperative Binding and Signal Transmission of the SARS-CoV-2 Spike Protein with Human Angiotensin-Converting Enzyme 2

International Journal of Molecular Sciences
Gennady Verkhivker


Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of the SARS-CoV and SARS-CoV-2 spike protein receptor binding domains with the ACE2 host receptor. Different from other computational studies, we systematically examine the molecular and energetic determinants of the binding mechanisms between SARS-CoV-2 and ACE2 proteins through the lens of coevolution, conformational dynamics, and allosteric interactions that conspire to drive binding interactions and signal transmission. Conformational dynamics analysis revealed the important differences in mobility of the binding interfaces for the SARS-CoV-2 sp...Continue Reading


Jul 1, 1985·Journal of Inorganic Biochemistry·P Bünning, J F Riordan
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·M A Martí-RenomA Sali
Jun 25, 2002·Journal of Molecular Biology·Raphael GueroisLuis Serrano
Dec 12, 2003·Bioinformatics·András Fiser, Andrej Sali
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Oct 7, 2004·International Review of Cytology·Nathalie MacoursRoger Huybrechts
Nov 19, 2004·Cellular and Molecular Life Sciences : CMLS·F J WarnerA J Turner
Nov 19, 2004·Cellular and Molecular Life Sciences : CMLS·J H KuhnM Farzan
Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuxian HeShibo Jiang
Jun 28, 2005·Nucleic Acids Research·Joost SchymkowitzLuis Serrano
Aug 27, 2005·Virology Journal·Samitabh ChakrabortiDimiter S Dimitrov
Sep 15, 2005·Bioinformatics·L C MartinL M Wahl
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 31, 2005·Nucleic Acids Research·Cathy H WuBaris Suzek
Mar 15, 2006·Biophysical Journal·Y DehouckM Rooman
Jul 18, 2006·Nucleic Acids Research·Narcis Fernandez-FuentesAndrás Fiser
Aug 15, 2006·Nature Structural & Molecular Biology·Nataliya PopovychCharalampos G Kalodimos
Sep 7, 2006·The Journal of Biological Chemistry·William C HwangRobert C Liddington
Jan 16, 2008·Journal of Computational Chemistry·Piotr Rotkiewicz, Jeffrey Skolnick
Oct 3, 2008·Proteins·Saikat Chakrabarti, Anna R Panchenko
Nov 20, 2009·Nature·Shiou-Ru Tzeng, Charalampos G Kalodimos
Jan 13, 2010·PloS One·Saikat Chakrabarti, Anna R Panchenko
May 27, 2010·Nucleic Acids Research·M L HekkelmanG Vriend
Apr 21, 2011·Bioinformatics·Joost Van DurmeFrederic Rousseau
Oct 30, 2012·Journal of Chemical Information and Modeling·Niels J Christensen, Kasper P Kepp
May 30, 2013·Nucleic Acids Research·Franco L SimonettiCristina Marino Buslje
Jun 1, 2013·Nucleic Acids Research·Yves DehouckDimitri Gilis
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Dec 4, 2013·Nucleic Acids Research·Robert D FinnAlex Bateman
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Nov 16, 2014·Bioinformatics·Baris E SuzekUNKNOWN UniProt Consortium
Jul 21, 2015·ELife·Anna Vangone, Alexandre Mjj Bonvin
Jul 9, 2013·Journal of Chemical Theory and Computation·Niels J Christensen, Kasper P Kepp
Dec 1, 2015·Journal of Chemical Theory and Computation·Michele Di PierroBenedict Leimkuhler
Dec 19, 2015·Bioinformatics·Leandro E LombardiLuciana Capece
May 1, 2016·Nucleic Acids Research·Debswapna BhattacharyaJianlin Cheng

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