The protein folding problem continues to attract intense research interest and remains as one of the unsolved problems to be carried over into the next millennium. Recent advances in the prediction of protein structures 1 in conjunction with the burgeoning structural genomics effort, 2 will in all likelihood bring a degree of closure to the protein structure prediction problem. However, there continues to be a significant division of opinion on the thermodynamic and kinetic aspects of folding, i.e., do proteins indeed fold to a ''free energy minimum,'' and if so, how do they find their way to unique predetermined folds? In addition to these traditional questions, increased attention is being focused on understanding protein folding in membranes and the linkage of protein misfolding to disease states. Studies on the mechanism of membrane protein folding and efforts in membrane protein structure prediction are likely to receive a boost as the number of available structures grow 3 and improved biochemical, thermodynamic, and genetic methods become available for characterizing protein interactions inside biological membranes. Active research on in vivo protein folding mechanisms promises to shed light on the fate of nascent polypeptide chains in a cellular environment.
The fourth annual Johns Hopkins meeting on protein folding focused on recent advances in a number of these areas. The meeting, held from March 13 to 17 at the Coolfont Resort and Conference Center in Berkeley Springs, West Virginia, was organized by Neil Clarke and Eaton Lattman. Five main sessions focused on the following: (1) The Folding Reaction; (2) In Vivo Folding and Amyloidogenesis; (3) Energetics; (4) Theoretical and Database Methods, and (5) Membrane Protein Folding. Session topics notwithstanding, the speakers brought forth specific issues likely to be addressed in ongoing research. These can be loosely classified into eight categories summarized below:
โข Transition states in protein folding.