Optimal combination of theory and experiment for the characterization of the protein folding landscape of S6: how far can a minimalist model go?
The detailed characterization of the overall free energy landscape associated with the folding process of a protein is the ultimate goal in protein folding studies. Modern experimental techniques provide accurate thermodynamic and kinetic measurements on restricted regions of a protein landscape. Although simplified protein models can access larger regions of the landscape, they are oftentimes built on assumptions and approximations that affect the accuracy of the results. We present a new methodology that allows to combine the complementary strengths of theory and experiment for a more complete characterization of a protein folding landscape. We prove that this new procedure allows a simplified protein model to reproduce remarkably well (correlation coefficient > 0.9) all experimental data available on free energies differences upon single mutations for S6 ribosomal protein and two circular permutants. Our results confirm and quantify the hypothesis, recently formulated on the basis of experimental data, that the folding landscape of protein S6 is strongly affected by an atypical distribution of contact energies.
Matysiak
Silvina
S
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Clementi
Cecilia
C
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019277:Entropy; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D008962:Models, Theoretical; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D038601:Ribosomal Protein S6 / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
D038601:Ribosomal Protein S6