Gradual development of protein-like global structures through functional selection.

This work focuses on streamlining the exploration of all possible sequences in an attempt to find polypeptides capable of folding into unique structures. Using a computer simulation, we have demonstrated the efficacy of constraining an 'active site' toward the correct configuration, in this case a particular conformation of a four-residue sequence, to bring about protein-like structure from a significant fraction of random sequences. The successive selections for a correct local configuration lead also to the gradual development of overall folding ability, helicity and compactness within 200 generations. The selection thus imposed alleviates an exhaustive search in sequence space.