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Understanding the determinants of stability and folding of small globular proteins from their energetics
Author(s) -
Tiana Guido,
Simona Fabio,
De Mori Giacomo M.S.,
Broglia Ricardo A.,
Colombo Giorgio
Publication year - 2004
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.03223804
Subject(s) - energetics , globular protein , globular cluster , protein folding , folding (dsp implementation) , stability (learning theory) , physics , protein evolution , chemistry , evolutionary biology , computational biology , biophysics , statistical physics , biology , crystallography , computer science , astrophysics , biochemistry , stars , thermodynamics , engineering , machine learning , electrical engineering , gene
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.
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