PMID- 33636637
OWN - NLM
STAT- MEDLINE
DCOM- 20210805
LR  - 20210805
IS  - 1476-928X (Electronic)
IS  - 1476-9271 (Linking)
VI  - 92
DP  - 2021 Jun
TI  - Evaluation of potential MHC-I allele-specific epitopes in Zika virus proteins and 
      the effects of mutations on peptide-MHC-I interaction studied using in silico 
      approaches.
PG  - 107459
LID - S1476-9271(21)00026-8 [pii]
LID - 10.1016/j.compbiolchem.2021.107459 [doi]
AB  - Zika virus (ZIKV) infection is a global health concern due to its association 
      with microcephaly and neurological complications. The development of a T-cell 
      vaccine is important to combat this disease. In this study, we propose ZIKV major 
      histocompatibility complex I (MHC-I) epitopes based on in silico screening 
      consensus followed by molecular docking, PRODIGY, and molecular dynamics (MD) 
      simulation analyses. The effects of the reported mutations on peptide-MHC-I 
      (pMHC-I) complexes were also evaluated. In general, our data indicate an 
      allele-specific peptide-binding human leukocyte antigen (HLA) and potential 
      epitopes. For HLA-B44, we showed that the absence of acidic residue Glu at P2, 
      due to the loss of the electrostatic interaction with Lys45, has a negative 
      impact on the pMHC-I complex stability and explains the low free energy estimated 
      for the immunodominant peptide E-4 (IGVSNRDFV). Our MD data also suggest the 
      deleterious effects of acidic residue Asp at P1 on the pMHC-I stability of HLA-B8 
      due to destabilization of the alpha-helix and beta-strand. Free energy estimation 
      further indicated that the mutation from Val to Ala at P9 of peptide E-247 
      (DAHAKRQTV), which was found exclusively in microcephaly samples, did not reduce 
      HLA-B8 affinity. In contrast, the mutation from Thr to Pro at P2 of the peptide 
      NS5-832 (VTKWTDIPY) decreased the interaction energy, number of intermolecular 
      interactions, and adversely affected its binding mode with HLA-A1. Overall, our 
      findings are important with regard to the design of T-cell peptide vaccines and 
      for understanding how ZIKV escapes recognition by CD8 + T-cells.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - da Costa, Aline Silva
AU  - da Costa AS
AD  - Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      RJ, 21941-902, Brazil; Instituto Nacional de Ciencia e Tecnologia de Biologia 
      Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      RJ, Brazil.
FAU - Fernandes, Tacio Vinicio Amorim
AU  - Fernandes TVA
AD  - Laboratorio de Macromoleculas, Diretoria de Metrologia Aplicada as Ciencias da 
      Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia - INMETRO, Duque 
      de Caxias, RJ, 25250-020, Brazil.
FAU - Bello, Murilo Lamim
AU  - Bello ML
AD  - Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      RJ, 21941-902, Brazil.
FAU - de Souza, Theo Luiz Ferraz
AU  - de Souza TLF
AD  - Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      RJ, 21941-902, Brazil; Instituto Nacional de Ciencia e Tecnologia de Biologia 
      Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 
      RJ, Brazil. Electronic address: theo@pharma.ufrj.br.
LA  - eng
PT  - Journal Article
DEP - 20210216
PL  - England
TA  - Comput Biol Chem
JT  - Computational biology and chemistry
JID - 101157394
RN  - 0 (Epitopes)
RN  - 0 (Peptides)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Alleles
MH  - Epitopes/genetics/*immunology
MH  - Major Histocompatibility Complex/genetics/*immunology
MH  - *Molecular Dynamics Simulation
MH  - Mutation
MH  - Peptides/genetics/*immunology
MH  - Viral Proteins/*genetics/immunology
MH  - Zika Virus/*chemistry/immunology
OTO - NOTNLM
OT  - Epitope prediction
OT  - Immunoinformatics
OT  - Molecular docking
OT  - Molecular dynamics simulation
OT  - Protein mutation
OT  - Zika virus
EDAT- 2021/02/27 06:00
MHDA- 2021/08/06 06:00
CRDT- 2021/02/26 20:17
PHST- 2020/06/14 00:00 [received]
PHST- 2021/02/06 00:00 [revised]
PHST- 2021/02/12 00:00 [accepted]
PHST- 2021/02/27 06:00 [pubmed]
PHST- 2021/08/06 06:00 [medline]
PHST- 2021/02/26 20:17 [entrez]
AID - S1476-9271(21)00026-8 [pii]
AID - 10.1016/j.compbiolchem.2021.107459 [doi]
PST - ppublish
SO  - Comput Biol Chem. 2021 Jun;92:107459. doi: 10.1016/j.compbiolchem.2021.107459. 
      Epub 2021 Feb 16.