PMID- 35816517
OWN - NLM
STAT- MEDLINE
DCOM- 20220725
LR  - 20230328
IS  - 1553-7358 (Electronic)
IS  - 1553-734X (Print)
IS  - 1553-734X (Linking)
VI  - 18
IP  - 7
DP  - 2022 Jul
TI  - Analysis of the docking property of host variants of hACE2 for SARS-CoV-2 in a 
      large cohort.
PG  - e1009834
LID - 10.1371/journal.pcbi.1009834 [doi]
LID - e1009834
AB  - The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute 
      respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening global health. 
      However, an understanding of the interaction of SARS-CoV-2 with human cells, 
      including the physical docking property influenced by the host's genetic 
      diversity, is still lacking. Here, based on germline variants in the UK Biobank 
      covering 502,543 individuals, we revealed the molecular interactions between 
      human angiotensin-converting enzyme 2 (hACE2), which is the representative 
      receptor for SARS-CoV-2 entry, and COVID-19 infection. We identified six nonsense 
      and missense variants of hACE2 from 2585 subjects in the UK Biobank covering 
      500000 individuals. Using our molecular dynamics simulations, three hACE2 
      variants from 2585 individuals we selected showed higher levels of binding free 
      energy for docking in the range of 1.44-3.69 kcal/mol. Although there are diverse 
      contributors to SARS-CoV-2 infections, including the mobility of individuals, we 
      analyzed the diagnosis records of individuals with these three variants of hACE2. 
      Our molecular dynamics simulations combined with population-based genomic data 
      provided an atomistic understanding of the interaction between hACE2 and the 
      spike protein of SARS-CoV-2.
FAU - Paik, Hyojung
AU  - Paik H
AUID- ORCID: 0000-0002-5803-0670
AD  - Division of Supercomputing, Center for supercomputing application and research, 
      Korea Institute of Science and Technology Information (KISTI), Daejeon, South 
      Korea.
AD  - Department of Data and HPC science, University of Science and Technology (UST), 
      Daejeon, South Korea.
FAU - Kim, Jimin
AU  - Kim J
AD  - Division of Supercomputing, Center for supercomputing application and research, 
      Korea Institute of Science and Technology Information (KISTI), Daejeon, South 
      Korea.
FAU - Seo, Sangjae
AU  - Seo S
AUID- ORCID: 0000-0002-3555-6223
AD  - Division of Supercomputing, Center for supercomputing application and research, 
      Korea Institute of Science and Technology Information (KISTI), Daejeon, South 
      Korea.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220711
PL  - United States
TA  - PLoS Comput Biol
JT  - PLoS computational biology
JID - 101238922
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - *Angiotensin-Converting Enzyme 2/genetics
MH  - *COVID-19/epidemiology/genetics
MH  - Humans
MH  - Peptidyl-Dipeptidase A/chemistry/genetics/metabolism
MH  - Protein Binding
MH  - SARS-CoV-2/genetics
MH  - Spike Glycoprotein, Coronavirus/chemistry
PMC - PMC9302733
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/07/12 06:00
MHDA- 2022/07/26 06:00
PMCR- 2022/07/11
CRDT- 2022/07/11 13:42
PHST- 2022/01/16 00:00 [received]
PHST- 2022/07/01 00:00 [accepted]
PHST- 2022/07/21 00:00 [revised]
PHST- 2022/07/12 06:00 [pubmed]
PHST- 2022/07/26 06:00 [medline]
PHST- 2022/07/11 13:42 [entrez]
PHST- 2022/07/11 00:00 [pmc-release]
AID - PCOMPBIOL-D-22-00067 [pii]
AID - 10.1371/journal.pcbi.1009834 [doi]
PST - epublish
SO  - PLoS Comput Biol. 2022 Jul 11;18(7):e1009834. doi: 10.1371/journal.pcbi.1009834. 
      eCollection 2022 Jul.