PROTEIN DESIGN IN A LATTICE MODEL OF HYDROPHOBIC AND POLAR AMINO-ACIDS

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The ap proach is used to design sequences of 48 hydrophobic and polar amino a cids on three-dimensional lattice structures. Previous studies employi ng a sequence-space Monte Carlo technique resulted in the successful d esign of one sequence in ten attempts. The present work also entails t he exploration of conformations that compete significantly with the ta rget structure for being its ground state. The design procedure is suc cessful in all the ten cases.