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Updated: May 10, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Relative free enthalpies for point mutations in two proteins with highly similar sequences but different folds
Niels Hansen1, Jane R Allison, Florian H Hodel
1Laboratory of Physical Chemistry, Swiss Federal Institute of Technology , ETH, CH-8093 Zürich, Switzerland.
Abstract:
Enveloping distribution sampling was used to calculate free-enthalpy changes associated with single amino acid mutations for a pair of proteins, GA95 and GB95, that show 95% sequence identity yet fold into topologically different structures. Of the L → A, I → F, and L → Y mutations at positions 20, 30, and 45, respectively, of the 56-residue sequence, the first and the last contribute the most to the free-enthalpy difference between the native and non-native sequence-structure combinations, in agreement with the experimental findings for this protein pair. The individual free-enthalpy changes are almost sequence-independent in the four-strand/one-helix structure, the stable form of GB95, while in the three-helix bundle structure, the stable form of GA95, an interplay between residues 20 and 45 is observed.
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