STATISTICAL-MECHANICS OF PROTEINS WITH EVOLUTIONARY SELECTED SEQUENCES

The requirement that the native structure of a protein be stable and k inetically accessible implies that it should correspond to a pronounce d energy minimum. Thus we expect the protein sequence not to be random but selected such that this is satisfied. This is achieved in our mod el by defining a ''selective temperature'' in sequence space and stati stically optimizing the sequence for the target conformation. Mean-fie ld replica calculations are presented for this model and the phase dia gram indicating the temperatures and selective temperatures at which t he transition to the native conformation occurs is obtained. The trans ition to the native state is shown to be a first-order one. A temperat ure range exists in which the target structure of selected sequences i s stable and kinetically accessible. It is shown that optimization at very low selective temperature leads to sequences with long-range corr elations which appear to be less capable of folding.