In silico energetic and molecular dynamic simulations studies demonstrate potential effect of the point mutations with implications for protein engineering in BDNF.
Int J Biol Macromol
; 271(Pt 1): 132247, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38750847
ABSTRACT
Protein engineering by directed evolution is time-consuming. Hence, in silico techniques like FoldX-Yasara for ∆∆G calculation, and SNPeffect for predicting propensity for aggregation, amyloid formation, and chaperone binding are employed to design proteins. Here, we used in silico techniques to engineer BDNF-NTF3 interaction and validated it using mutations with known functional implications for NGF dimer. The structures of three mutants representing a positive, negative, or neutral ∆∆G involving two interface residues in BDNF and two mutations representing a neutral and positive ∆∆G in NGF, which is aligned with BDNF, were selected for molecular dynamics (MD) simulation. Our MD results conclude that the secondary structure of individual protomers of the positive and negative mutants displayed a similar or different conformation from the NTF3 monomer, respectively. The positive mutants showed fewer hydrophobic interactions and higher hydrogen bonds compared to the wild-type, negative, and neutral mutants with similar SASA, suggesting solvent-mediated disruption of hydrogen-bonded interactions. Similar results were obtained for mutations with known functional implications for NGF and BDNF. The results suggest that mutations with known effects in homologous proteins could help in validation, and in silico directed evolution experiments could be a viable alternative to the experimental technique used for protein engineering.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
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Mutação Puntual
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Fator Neurotrófico Derivado do Encéfalo
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Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia