Local interactions dominate folding in a simple protein model.

Abstract

Recent computational studies of simple models of protein folding have concluded that a pronounced energy minimum (i.e. large gap in energy between low-energy states of the model) is a necessary and sufficient condition to ensure folding of a sequence to its lowest-energy conformation. Here, we show that this conclusion strongly depends on the particular temperature scheme selected to govern the simulations. On the other hand, we show that there is a dominant factor determining if a sequence is foldable. That is, the strength of possible interactions between residues close in the sequence. We show that sequences with many possible strong local interactions (either favorable or, more surprisingly, a mixture of strong favorable and unfavorable ones) are easy to fold. Progressively increasing the strength of such local interactions makes sequences easier and easier to fold. These results support the idea that initial formation of local substructures is important to the foldability of real proteins.