WFU Physics Colloquium

Under physiological conditions, a protein undergoes a spontaneous disorder ↔ order transition called folding. The protein polymer is highly 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/co-solvent conditions. From the latter, we know the structures of ~35,000 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 selfassembly remains an open question -- perhaps the most fundamental open question in biochemistry.

In the classical view, anchored in ideas and experiments developed over the past halfcentury, the energetics of sidechain interactions dominate the folding process, driving the chain to self-organize under folding conditions. In contrast to this view, an alternative model is proposed that inverts the prevailing sidechain/backbone paradigm. Here, the energetics of backbone hydrogen bonds dominate the folding process, with pre-organization occurring in the unfolded state. Then, under folding conditions, the resultant fold is selected from a limited repertoire of structural possibilities, each corresponding to a distinct hydrogen-bonded arrangement of α-helices and/or strands of β-sheet.

This seminar is sponsored jointly by the Physics Department and the Center for Structural Biology at Wake Forest University.

100 Olin Physical Laboratory, 7507 Reynolda Station Wake Forest University Winston-Salem, NC 27109-7507 Phone: (336) 758-5337, FAX: (336) 758-6142 E-mail: wfuphys@wfu.edu	Quick Links Academics Research People Colloquia Info Physics