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 structur es. Using a computer simulation, we have demonstrated the efficacy of const raining an 'active site' toward the correct configuration, in this case a p articular conformation of a four-residue sequence, to bring about protein-l ike structure from a significant fraction of random sequences. The successi ve selections for a correct local configuration lead also to the gradual de velopment of overall folding ability, helicity and compactness within 200 g enerations, The selection thus imposed alleviates an exhaustive search in s equence space.