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Biophys J. 2005 Dec;89(6):3714-20. Epub 2005 Sep 8.

Predicting the tolerance of proteins to random amino acid substitution.

Author information

1
Keck Graduate Institute of Applied Life Sciences, Claremont, California, USA. cwilke@mail.utexas.edu

Abstract

We have recently proposed a thermodynamic model that predicts the tolerance of proteins to random amino acid substitutions. Here we test this model against extensive simulations with compact lattice proteins, and find that the overall performance of the model is very good. We also derive an approximate analytic expression for the fraction of mutant proteins that fold stably to the native structure, Pf(m), as a function of the number of amino acid substitutions m, and present several methods to estimate the asymptotic behavior of Pf(m) for large m. We test the accuracy of all approximations against our simulation results, and find good overall agreement between the approximations and the simulation measurements.

PMID:
16150971
PMCID:
PMC1366941
DOI:
10.1529/biophysj.105.062125
[Indexed for MEDLINE]
Free PMC Article

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