Sugita Y, Kitao A, Go N
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Fold Des. 1998;3(3):173-81. doi: 10.1016/S1359-0278(98)00025-X.
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.
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.
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.
