Protein Folding

Our research is focused primarily on protein folding, the spontaneous disorder ⇌ order transition that occurs under physiological conditions. The protein polymer is flexible when unfolded but adopts its unique native, three dimensional structure when folded. Current experimental knowledge comes primarily from thermodynamic measurements in solution or the structures of individual molecules, elucidated by either X-ray crystallography or NMR spectroscopy. From the former, we know the enthalpy, entropy, and free energy differences between the folded and unfolded forms of hundreds of proteins under a variety of solvent/cosolvent conditions. From the latter, we know the structures of approximately 100,000 proteins, which are built on scaffolds of hydrogen-bonded structural elements, α-helix and β-sheet. Anfinsen showed that the amino acid sequence alone is sufficient to determine a protein’s structure, but the molecular mechanism responsible for self-assembly remains a fundamental open question in chemical biology. (“A backbone-based theory of protein folding” Proc Nat. Acad. Sci. 103: 16623-16633.)

protein folding