OmniVira

Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions.

Yingjie Wang1 Meiyi Liu1,2 Jiali Gao3,4,2,5,6
Affiliations 6 institutions
  1. Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen 518055, China.
  2. College of Chemical Biology and Biotechnology, Beijing University Shenzhen Graduate School, Shenzhen 518055, China.
  3. Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen 518055, China
  4. [email protected].
  5. Department of Chemistry, University of Minnesota, Minneapolis, MN 55455.
  6. Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455.
PMID32503918 DOI10.1073/pnas.2008209117 Year2020 Journal Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A Languageeng Publication statusActive
Active Last checked 2026-10-06 03:30:27 Source: NCBI PubMed

Abstract

Molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein-protein interactions between the common receptor protein angiotensin converting enzyme 2 (ACE2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [A. E. Gorbalenya et al., Nat. Microbiol. 5, 536-544 (2020)] that causes coronavirus disease 2019 (COVID-19) [P. Zhou et al., Nature 579, 270-273 (2020)] and the SARS coronavirus in the 2002-2003 (SARS-CoV) [T. Kuiken et al., Lancet 362, 263-270 (2003)] outbreak. Analysis of the dynamic trajectories reveals that the binding interface consists of a primarily hydrophobic region and a delicate hydrogen-bonding network in the 2019 novel coronavirus. A key mutation from a hydrophobic residue in the SARS-CoV sequence to Lys417 in SARS-CoV-2 creates a salt bridge across the central hydrophobic contact region, which along with polar residue mutations results in greater electrostatic complementarity than that of the SARS-CoV complex. Furthermore, both electrostatic effects and enhanced hydrophobic packing due to removal of four out of five proline residues in a short 12-residue loop lead to conformation shift toward a more tilted binding groove in the complex in comparison with the SARS-CoV complex. On the other hand, hydrophobic contacts in the complex of the SARS-CoV-neutralizing antibody 80R are disrupted in the SARS-CoV-2 homology complex model, which is attributed to failure of recognition of SARS-CoV-2 by 80R.

molecular dynamics 11 protein–protein interaction 1 relative free energy of binding 0 SARS-CoV-2 556 Protein Binding 194 Amino Acids 14 Angiotensin-Converting Enzyme 2 178 Antibodies, Neutralizing 80 Antibodies, Viral 216 Betacoronavirus 79 Coronavirus Infections 172 COVID-19 427 Humans 1455 Hydrogen Bonding 2 Hydrophobic and Hydrophilic Interactions 2 Models, Molecular 99 Molecular Dynamics Simulation 21 Pandemics 109 Peptidyl-Dipeptidase A 58 Pneumonia, Viral 42 Protein Domains 45 Receptors, Virus 208 SARS-CoV-2 456 Static Electricity 1

Evidence records

0 total

No structured evidence records are linked to this article.