Relative stability of de novo four-helix bundle proteins: insights from coarse grained molecular simulations.
Protein Sci
; 20(5): 818-26, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21344535
ABSTRACT
We use a recently developed coarse-grained computational model to investigate the relative stability of two different sets of de novo designed four-helix bundle proteins. Our simulations suggest a possible explanation for the experimentally observed increase in stability of the four-helix bundles with increasing sequence length. In details, we show that both short subsequences composed only by polar residues and additional nonpolar residues inserted, via different point mutations in ad hoc positions, seem to play a significant role in stabilizing the four-helix bundle conformation in the longer sequences. Finally, we propose an additional mutation that rescues a short amino acid sequence that would otherwise adopt a compact misfolded state. Our work suggests that simple computational models can be used as a complementary tool in the design process of de novo proteins.
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1
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Proteínas
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Modelos Moleculares
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Estrutura Secundária de Proteína
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article