Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations.
Proc Natl Acad Sci U S A
; 111(43): 15396-401, 2014 Oct 28.
Article
en En
| MEDLINE
| ID: mdl-25313044
ABSTRACT
The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity has proven challenging. We calculate this loss using molecular dynamic simulations of both the native protein and a realistic denatured state ensemble. For ubiquitin, the total change in entropy is TΔSTotal = 1.4 kcalâ
mol(-1) per residue at 300 K with only 20% from the loss of side-chain entropy. Our analysis exhibits mixed agreement with prior studies because of the use of more accurate ensembles and contributions from correlated motions. Buried side chains lose only a factor of 1.4 in the number of conformations available per rotamer upon folding (ΩU/ΩN). The entropy loss for helical and sheet residues differs due to the smaller motions of helical residues (TΔShelix-sheet = 0.5 kcalâ
mol(-1)), a property not fully reflected in the amide N-H and carbonyl C=O bond NMR order parameters. The results have implications for the thermodynamics of folding and binding, including estimates of solvent ordering and microscopic entropies obtained from NMR.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Espectroscopía de Resonancia Magnética
/
Pliegue de Proteína
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Entropía
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Ubiquitina
Idioma:
En
Año:
2014
Tipo del documento:
Article