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, ΔΔG, on the denatured-state structure, extended and native-like conformations are employed as initial conformations in the denatured-state simulations.

Results: Calculated values of ΔΔG 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 ΔΔG 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 α domain in which Ile23 is included is considerably structured even in the denatured state.