In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design.
A29 protein
MPXV
in vitro affinity maturation
nanobody
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
22
08
2023
revised:
20
09
2023
accepted:
25
09
2023
medline:
23
10
2023
pubmed:
14
10
2023
entrez:
14
10
2023
Statut:
epublish
Résumé
Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.
Identifiants
pubmed: 37836685
pii: molecules28196838
doi: 10.3390/molecules28196838
pmc: PMC10574621
pii:
doi:
Substances chimiques
Single-Domain Antibodies
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Kai Xiao
ID : 81871521
Organisme : Kai Xiao
ID : 21QNPY052
Organisme : Mingxue Sun
ID : 82103885
Organisme : Mingxue Sun
ID : 21ZR1477700
Organisme : Qingqiang Xu
ID : 2022YFC2602900
Organisme : Qingqiang Xu
ID : 21QNPY036
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