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Modeling of denatured state for calculation of the electrostatic contribution to protein stability
Author(s) -
Kundrotas Petras J.,
Karshikoff Andrey
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.4690102
Subject(s) - barnase , stability (learning theory) , chemistry , denaturation (fissile materials) , electrostatics , protein stability , sequence (biology) , thermodynamics , chemical physics , statistical physics , crystallography , physics , ribonuclease , computer science , biochemistry , rna , machine learning , nuclear chemistry , gene
Existing models of the denatured state of proteins consider only one possible spatial distribution of protein charges and therefore are applicable to a limited number of cases. In this article, a more general framework for the modeling of the denatured state is proposed. It is based on the assumption that the titratable groups of an unfolded protein can adopt a quasi‐random distribution restricted by the protein sequence. The model was applied for the calculations of electrostatic interactions in two proteins, barnase and N‐terminal domain of the ribosomal protein L9. The calculated free energy of denaturation, Δ G (pH), reproduces the experimental data better than the commonly used null approximation (NA). It was shown that the seemingly good agreement with experimental data obtained by NA originates from the compensatory effect between the pairwise electrostatic interactions and the desolvation energy of the individual sites. It was also found that the ionization properties of denatured proteins are influenced by the protein sequence.