Model for calculation of electrostatic interactions in unfolded proteins.
An approach for the calculation of electrostatic interactions and titration properties of unfolded polypeptide chains (denatured proteins) is proposed. It is based on a simple representation of the denatured proteins as a state with titratable sites distributed on the surface of a sphere, radius of which is assumed to be equal to the radius of gyration, R(g), of an unfolded molecule. Distances between the charges, d, obey constraints arising from the protein sequence. Criteria for evaluation of the parameters R(g) and d were obtained from computer simulations on a polypeptide consisting of 20 identical amino acids (polylysine). The model was applied for calculation of titration curves of denatured barnase and staphylococcal nuclease. It was demonstrated that the approach proposed gives considerably better agreement with the experimental data than the commonly used null approximation. It was also found that titration properties of denatured proteins are slightly, but distinguishably influenced by the amino-acid sequence of the protein.
Kundrotas
P J
PJ
Department of Biosciences at Novum Research Park, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden.
Karshikoff
A
A
D001426:Bacterial Proteins; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D008836:Micrococcal Nuclease / Q000737:chemistry; D008956:Models, Chemical; D015233:Models, Statistical; D008962:Models, Theoretical; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000737:chemistry
D001426:Bacterial Proteins; D011506:Proteins; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D008836:Micrococcal Nuclease