Protein Folding: From Lattice Models to Real Proteins

Recent progress in understanding the principals of protein folding by a study of a simple lattice model stimulates further research aimed at bridging a gap between theoretical and experimental protein folding and at protein structure prediction. Using a lattice model we studied folding kinetics of two model proteins and observed qualitatively different scenarios: one folds rapidly without intermediates by a two-state mechanism, whereas the other one folds much slower exhibiting several misfolded intermediates. Analysis showed the intermediates are not required for folding, but instead slow down and derail it. Next, using the same model, we simulated protein evolution toward fast folding and observed that the increase of the folding rate was associated with considerable stabilization of the folding nucleus without stabilization of the rest of the molecule. After rapid folding is achieved, residues contributing to the nucleus became conserved. Analysis of real proteins points out that fo..