PMID- 35788229
OWN - NLM
STAT- MEDLINE
DCOM- 20220715
LR  - 20220718
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 24
IP  - 27
DP  - 2022 Jul 13
TI  - In silico study on the effects of disulfide bonds in ORF8 of SARS-CoV-2.
PG  - 16876-16883
LID - 10.1039/d2cp01724e [doi]
AB  - The COVID-19 epidemic, caused by virus SARS-CoV-2, has turned into a pandemic and 
      threatened everyone's health for the past two years. In SARS-CoV-2, ORF8 is one 
      of the most important accessory proteins with a role in immune modulation. There 
      are multiple disulfide bonds in the wild type (WT) ORF8. Here, we present an in 
      silico study on the effects of the disulfide bonds in ORF8 on the aspects of the 
      structural properties and binding properties with the human leukocyte antigen 
      (HLA-A). We first define five possible states for ORF8 with different disulfide 
      bond reduction schemes. For each state, we collect the conformational ensemble 
      using molecular dynamics (MD) simulations in an explicit solvent. From the 
      analysis of the structural properties, we find that the reduction of the 
      disulfide bonds has small effects on the global properties but much larger 
      effects on the ORF8-specific region that is located on the surface of the ORF8 
      dimer. Interestingly, we find that the dimer does not break into two monomers at 
      room temperature even if all the disulfide bonds get reduced. Further, we 
      investigate the role of the disulfide bonds in the interactions with the human 
      leukocyte antigen (HLA) by performing docking between HLA-A and the 
      conformational ensembles of ORF8 in different states. We give predictions on the 
      preferred binding sites for each state and validate the predictions for the WT 
      dimer with the experimental data on epitopes. In the end, we evaluate the 
      stability of the complexes formed between HLA-A and ORF8 in each state using MD 
      simulations. Our observations can provide inspiration for inhibitor/drug design 
      against ORF8 based on the binding pathway with HLA-A.
FAU - Cheng, Yadi
AU  - Cheng Y
AD  - Center for Quantum Technology Research, Key Laboratory of Advanced Optoelectronic 
      Quantum Architecture and Measurements (MOE), School of Physics, Beijing Institute 
      of Technology, Beijing, 100081, China.
FAU - Peng, Xubiao
AU  - Peng X
AUID- ORCID: 0000-0002-6494-9560
AD  - Center for Quantum Technology Research, Key Laboratory of Advanced Optoelectronic 
      Quantum Architecture and Measurements (MOE), School of Physics, Beijing Institute 
      of Technology, Beijing, 100081, China.
AD  - Beijing Academy of Quantum Information Sciences, Beijing 100193, China. 
      xubiaopeng@bit.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220713
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Disulfides)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (ORF8 protein, SARS-CoV-2)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - *COVID-19
MH  - Disulfides
MH  - HLA Antigens
MH  - HLA-A Antigens
MH  - Humans
MH  - *SARS-CoV-2
MH  - Viral Proteins/*metabolism
EDAT- 2022/07/06 06:00
MHDA- 2022/07/16 06:00
CRDT- 2022/07/05 18:19
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/16 06:00 [medline]
PHST- 2022/07/05 18:19 [entrez]
AID - 10.1039/d2cp01724e [doi]
PST - epublish
SO  - Phys Chem Chem Phys. 2022 Jul 13;24(27):16876-16883. doi: 10.1039/d2cp01724e.