Predicting the tolerance of proteins to random amino acid substitution.
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.
Wilke
Claus O
CO
Keck Graduate Institute of Applied Life Sciences, Claremont, California, USA. cwilke@mail.utexas.edu
Bloom
Jesse D
JD
Drummond
D Allan
DA
Raval
Alpan
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000032:analysis / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D011506:Proteins