A determinable but unresolved problem

Abstract

PROTEIN FOLDING(1) IS A REAL challenge that nature has presented to molecular physicists and molecular biologists because each protein knows how to fold, but nobody understands how this is done. There are two basic problems in protein folding: one is that of intermediate states, which correspond to the local minima of free energy on a folding pathway, and the other is that of transition states, which correspond to the potential energy barriers on this pathway. There is one very important feature of protein structures. Each protein has its own amino acid sequence and its own detailed tertiary structure based on the specific tight packing of its side chains. However, analogous proteins from different species and proteins with slightly different functions can have a large variety of sequences and tertiary structures, but still share a common architectural motive (“tertiary fold” or “folding pattern”) (2). For instance, different globins have only two sites occupied by invariant amino acids, but all of them share the same “globin fold.” There are also the “immunoglobin fold,” the “trypsin fold,” and many others. Moreover, many quite different proteins can share similar folding patterns, suggesting that the number of folding patterns is much smaller than the