Computational analysis of thermal stability: effect of Ile-->Val mutations in human lysozyme.
BACKGROUND
Free energy calculations are carried out to study the change of thermal stability caused by Ile23-->Val, Ile56-->Val, Ile89-->Val and Ile106-->Val mutations in human lysozyme. In order to examine the dependence of the free energy difference, DeltaDeltaG, on the denatured-state structure, extended and native-like conformations are employed as initial conformations in the denatured-state simulations.


RESULTS
Calculated values of DeltaDeltaG for the mutations, Ile56-->Val, Ile89-->Val and Ile106-->Val, were in good agreement with experimental values when the native-like structure was employed in the respective denatured-state simulations. In the case of Ile23-->Val, a considerable difference between the calculated and experimental values of DeltaDeltaG was observed.


CONCLUSIONS
The physical nature of Ile56-->Val, Ile89-->Val and Ile106-->Val mutations was rationally characterized by a free energy component analysis. It is suggested that the alpha domain in which Ile23 is included is considerably structured even in the denatured state.
Sugita
Y
Y
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Kitao
A
A
Go
N
N
D000465:Algorithms; D003198:Computer Simulation; D004795:Enzyme Stability; D006358:Hot Temperature; D006801:Humans; D007532:Isoleucine / Q000737:chemistry* / Q000235:genetics; D008956:Models, Chemical; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D011489:Protein Denaturation; D013816:Thermodynamics; D014633:Valine / Q000737:chemistry* / Q000235:genetics
D007532:Isoleucine; D009113:Muramidase; D014633:Valine