title: Modeling of denatured state for calculation of the electrostatic contribution to protein stability.
abstract: 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, DeltaG(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.
authors.affiliation: Department of Biosciences, Karolinska Institute, SE-14157 Huddinge, Sweden.
authors.forename: Petras J
authors.initials: PJ
authors.lastname: Kundrotas
authors.forename: Andrey
authors.initials: A
authors.lastname: Karshikoff
mesh_terms: D001426:Bacterial Proteins; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D011506:Proteins; D012269:Ribosomal Proteins; C049650:ribosomal protein L9; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease