Meanfield approach to the thermodynamics of protein-solvent systems with application to p53.
We present a meanfield theoretical approach for studying protein-solvent interactions. Starting with the partition function of the system, we develop a field theory by introducing densities for the different components of the system. At this point, protein-solvent interactions are introduced following the inhomogeneous Flory-Huggins model for polymers. Finally, we calculate the free energy in a meanfield approximation. We apply this method to study the stability of the tetramerization domain of the tumor suppressor protein p53 when subjected to site-directed mutagenesis. The four chains of this protein are held together by hydrophobic interactions, and some mutations can weaken this bond while preserving the secondary structure of the single protein chains. We find good qualitative agreement between our numerical results and experimental data, thus encouraging the use of this method as a guide in designing experiments.
Völkel
A R
AR
Xerox Research Centre of Canada, Mississauga, Ontario L5K 2L1, Canada. avolhel@pavc.xerox.com
Noolandi
J
J
D019943:Amino Acid Substitution; D001665:Binding Sites; D046911:Macromolecular Substances; D008958:Models, Molecular; D008962:Models, Theoretical; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D012997:Solvents; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D012997:Solvents; D016159:Tumor Suppressor Protein p53