LOCAL INTERACTIONS DOMINATE FOLDING IN A SIMPLE PROTEIN MODEL

Recent computational studies of simple models of protein folding have concluded that a pronounced energy minimum (i.e. large gap in energy b etween low-energy states of the model) is a necessary and sufficient c ondition to ensure folding of a sequence to its lowest-energy conforma tion. Here, we show that this conclusion strongly depends on the parti cular temperature scheme selected to govern the simulations. On the ot her hand, we show that there is a dominant factor determining if a seq uence is foldable. That is, the strength of possible interactions betw een residues close in the sequence. We show that sequences with many p ossible strong local interactions (either favorable or, more surprisin gly, a mixture of strong favorable and unfavorable ones) are easy to f old. Progressively increasing the strength of such local interactions makes sequences easier and easier to fold. These results support the i dea that initial formation of local substructures is important to the foldability of real proteins. (C) 1996 Academic Press Limited