Predicting the tertiary structure of a lattice designed model protein from its primary structure.

Through systematic studies of lattice Monte Carlo simulations of thefolding of designed heteropolymers, we have identified a hierarchy ofspecific elementary phenomena which control the way single domain proteinfold: a) formation of few, local elementary structures, b) creation ofthe (post-critical) folding nucleus through the assemblage together ofthe local elementary structures, c) relaxation of the remaining aminoacids to the native conformation. These results, which are consistentwith a two-state kinetics of the folding of small, single domain proteins,where the local elementary structures and the folding nucleus can be viewedas hidden intermediates along the reaction pathway, provide the basis fora strategy to read the tertiary structure of a protein from its aminoacid sequence.