HOW MANY PROTEIN-FOLDING MOTIFS ARE THERE

As the three-dimensional structures of more and more proteins are dete rmined by experiment, discovering substantially novel folding motifs b ecomes ever rarer. The natural question is how many motifs are there a nd how many have already been found? In order to answer this in at lea st one plausible and well-defined sense, we have chosen a quantitative measure of conformational similarity, rho (based on optimal rigid bod y superposition), and a means of generating all possible three-dimensi onal chain conformations using the discrete cosine transform. How many different folding motifs there are then depends on the specified cuto ff in rho and on the flexibility allowed for the model polypeptide cha in. For single chain proteins having no more than about 170 residues a nd which are not beta-barrels, there are only about 128 motifs that di ffer by rho > 1.0 (an extremely vague level of similarity), of which s o far only 100 have been seen experimentally The remaining 28 can be v iewed as very low-resolution models of either undiscovered novel folds or violations of unknown principles of protein folding. (C) 1995 Acad emic Press Limited