DOI: 10.1073/pnas.2008209117
论文题名: Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions
作者: Wang Y. ; Liu M. ; Gao J.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2020
卷: 117, 期: 25 起始页码: 13967
结束页码: 13974
语种: 英语
英文关键词: Molecular dynamics
; Protein-protein interaction
; Relative free energy of binding
; SARS-CoV-2
Scopus关键词: angiotensin converting enzyme 2
; hydrogen
; lysine
; neutralizing antibody
; proline
; virus antibody
; amino acid
; dipeptidyl carboxypeptidase
; protein binding
; virus receptor
; amino acid sequence
; antigen binding
; Article
; coronavirus disease 2019
; epidemic
; hydrogen bond
; hydrophobicity
; illness trajectory
; molecular dynamics
; priority journal
; protein conformation
; protein domain
; protein protein interaction
; protein structure
; receptor binding
; sequence homology
; Severe acute respiratory syndrome coronavirus 2
; static electricity
; Betacoronavirus
; chemical phenomena
; chemistry
; coronavirus disease 2019
; Coronavirus infection
; human
; hydrogen bond
; metabolism
; molecular model
; pandemic
; physiology
; Severe acute respiratory syndrome coronavirus 2
; virus pneumonia
; Amino Acids
; Antibodies, Neutralizing
; Antibodies, Viral
; Betacoronavirus
; Coronavirus Infections
; Humans
; Hydrogen Bonding
; Hydrophobic and Hydrophilic Interactions
; Models, Molecular
; Molecular Dynamics Simulation
; Pandemics
; Peptidyl-Dipeptidase A
; Pneumonia, Viral
; Protein Binding
; Protein Domains
; Receptors, Virus
; Static Electricity
英文摘要: 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 SARSCoV 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 SARSCoV- 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. © 2020 National Academy of Sciences. All rights reserved. Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163458
Appears in Collections: 气候变化与战略
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作者单位: Wang, Y., Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, 518055, China; Liu, M., Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, 518055, China, College of Chemical Biology and Biotechnology, Beijing University Shenzhen Graduate School, Shenzhen, 518055, China; Gao, J., Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen, 518055, China, College of Chemical Biology and Biotechnology, Beijing University Shenzhen Graduate School, Shenzhen, 518055, China, Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, United States, Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, United States
Recommended Citation:
Wang Y.,Liu M.,Gao J.. Enhanced receptor binding of SARS-CoV-2 through networks of hydrogen-bonding and hydrophobic interactions[J]. Proceedings of the National Academy of Sciences of the United States of America,2020-01-01,117(25)