Predicting the protein folding nucleus from a sequence

Understanding the mechanism of protein folding mould allow prediction of th e three-dimensional structure from sequence data alone. It has been shown t hat small proteins fold in a small number of kinetic steps and that signifi cantly populated intermediate states exist for some of them. Studies of the se intermediates have demonstrated the existence of specific interactions e stablished during the initial stages of folding, Comparison of the amino ac ids participating in these specific and essential interactions and constitu ting the folding nucleus with conserved hydrophobic positions of a given fo ld shows a striking correspondence, This finding opens the perspective of p redicting the folding nucleus knowing only a set of divergent sequences of a protein family. (C) 1999 Federation of European Biochemical Societies.