SUCCESSFUL PROTEIN FOLD RECOGNITION BY OPTIMAL SEQUENCE THREADING VALIDATED BY RIGOROUS BLIND TESTING

Analysis of the results of the recent protein structure prediction exp eriment for our method shows that we achieved a high level of success, Of the 18 available prediction targets of known structure, the assess ors have identified 11 chains which either entirely match a previously known fold, or which partially match a substantial region of a known fold, Of these 11 chains, we made predictions for 9, and correctly ass igned the folds in 5 cases, We have also identified a further 2 chains which also partially match known folds, and both of these were correc tly predicted, The success rate for our method under blind testing is therefore 7 out of 11 chains, A further 2 folds could have easily been recognized but failed due to either overzealous filtering of potentia l matches, or to simple human error on our part. One of the two target s for which we did not submit a prediction, prosubtilisin, would not h ave been recognized by our usual criteria, but even in this case, it i s possible that a correct prediction could have been made by consideri ng a combination of pairwise energy and solvation energy Z-scores. Ins pection of the threading alignments for the (alpha beta)(8) barrels pr ovides clues as to how fold recognition by threading works, in that th ese folds are recognized by parts rather than as a whole. The prospect s for developing sequence threading technology further is discussed. ( C) 1995 Wiley-Liss, Inc.