Accurate and Rigorous Prediction of the Changes in Protein Free Energies in a Large-Scale Mutation Scan.
Angew Chem Int Ed Engl
; 55(26): 7364-8, 2016 06 20.
Article
en En
| MEDLINE
| ID: mdl-27122231
ABSTRACT
The prediction of mutation-induced free-energy changes in protein thermostability or protein-protein binding is of particular interest in the fields of protein design, biotechnology, and bioengineering. Herein, we achieve remarkable accuracy in a scan of 762 mutations estimating changes in protein thermostability based on the first principles of statistical mechanics. The remaining error in the free-energy estimates appears to be due to three sources in approximately equal parts, namely sampling, force-field inaccuracies, and experimental uncertainty. We propose a consensus force-field approach, which, together with an increased sampling time, leads to a free-energy prediction accuracy that matches those reached in experiments. This versatile approach enables accurate free-energy estimates for diverse proteins, including the prediction of changes in the melting temperature of the membrane protein neurotensin receptorâ
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Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Termodinámica
/
Receptores de Neurotensina
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania