We have developed a computer program called CORE that predicts the primary sequences that give rise to highly stable proteins. With this program, we have the flexibility to design any number of stable proteins with only the backbone structure and solvent exposed residues as input. CORE relies on a combination of Monte Carlo and simulated annealing techniques and simple packing criteria to find stable structures.

We have implemented the program in the design of highly stable synthetic four-helix peptides. The peptides are synthesized using standard solid-phase techniques. Techniques we use to characterize the peptides include circular dichroism, UV-vis, and fluorescence spectroscopy, HPLC, 1D and 2D NMR, and mass spectroscopy. Electron-transfer rates are measured using steady-state and time-resolved absorption and emission (TCSPC) techniques.

(Collaborative work with Ramy Farid)