The results of minimal model calculations indicate that the stability and the kinetic accessibility of the native state of small globular proteins are controlled by few hot sites. By means of molecular dynamics simulations around the native conformation, which describe the protein and the surrounding solvent at the all-atom level, an accurate and compact energetic map of the native state of the protein is generated. This map is further simplified by means of an eigenvalue decomposition. The components of the eigenvector associated with the lowest eigenvalue indicate which hot sites are likely to be responsible for the stability and for the rapid folding of the protein. The comparison of the results of the model with the findings of mutagenesis experiments performed for four small proteins show that the eigenvalue decomposition method is able to identify between 60% and 80% of these (hot) sites.

Understanding the determinants of stability and folding of small globular proteins from their energetics / G. Tiana, F. Simona, G. M. S. De Mori, R. A. Broglia, G. Colombo. - In: PROTEIN SCIENCE. - ISSN 0961-8368. - 13:1(2004), pp. 113-124. [10.1110/ps.03223804]

Understanding the determinants of stability and folding of small globular proteins from their energetics

G. Tiana
Primo
;
R.A. Broglia
Penultimo
;
2004

Abstract

The results of minimal model calculations indicate that the stability and the kinetic accessibility of the native state of small globular proteins are controlled by few hot sites. By means of molecular dynamics simulations around the native conformation, which describe the protein and the surrounding solvent at the all-atom level, an accurate and compact energetic map of the native state of the protein is generated. This map is further simplified by means of an eigenvalue decomposition. The components of the eigenvector associated with the lowest eigenvalue indicate which hot sites are likely to be responsible for the stability and for the rapid folding of the protein. The comparison of the results of the model with the findings of mutagenesis experiments performed for four small proteins show that the eigenvalue decomposition method is able to identify between 60% and 80% of these (hot) sites.
Settore FIS/03 - Fisica della Materia
2004
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/141357
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 79
  • ???jsp.display-item.citation.isi??? 73
social impact