Prediction of the activity and stability effects of site-directed mutagenesis on a protein core

Vangunsteren, WF and Mark, AE (1992) Prediction of the activity and stability effects of site-directed mutagenesis on a protein core. Journal of Molecular Biology, 227 2: 389-395. doi:10.1016/0022-2836(92)90895-Q


Author Vangunsteren, WF
Mark, AE
Title Prediction of the activity and stability effects of site-directed mutagenesis on a protein core
Journal name Journal of Molecular Biology   Check publisher's open access policy
ISSN 0022-2836
Publication date 1992-09-20
Sub-type Article (original research)
DOI 10.1016/0022-2836(92)90895-Q
Volume 227
Issue 2
Start page 389
End page 395
Total pages 7
Language eng
Subject 2406 Virology
Abstract When theoretical methods are used to predict the properties of a given system, such as the effects of the substitution of a specific amino acid on the activity or stability of a protein as a whole, the accuracy of the prediction is directly dependent on the validity of the underlying model. A common error, however, is to attempt to improve a basically crude model by performing one aspect of the calculation in a rigorous manner. The accuracy of the model as a whole will remain limited by the crudest approximation or weakest assumption. To demonstrate the principle that nothing can be gained by performing extensive calculations using a basically crude underlying model we compare the predictive power of three models in relation to activity and stability data for 78 triple-site sequence variants of the λ-repressor protein. This system has recently been analysed in terms of a conceptionally simple, but computationally elaborate model for the prediction of the energy of a protein in which amino acid residues in the core of the protein have been mutated. We show that comparable, if not better agreement with the experimental data can be reached using either of two much simpler models, based on straightforward structural considerations, which do not require elaborate calculations on a computer.
Keyword computer simulation
prediction
protein activity
protein stability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 38 times in Scopus Article | Citations
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