COMPUTER DESIGN OF IDEALIZED BETA-MOTIFS

A lattice model of protein conformation and dynamics is used to explor e the requirements for the de novo folding from an arbitrary random co il state of idealized models of four and six-member beta-barrels. A nu mber of possible conjectures for the factors giving rise to the struct ural uniqueness of globular proteins are examined. These include the r elative role of generic hydrophilic/hydrophobic amino acid patterns, t he relative importance of the specific identity of the hydrophobic ami no acids that form the core of the protein and the possible role playe d by polar groups in destabilizing alternative, misfolded conformation s. These studies may also provide some insights into the relative impo rtance of short range interactions, cooperative hydrogen bonding and t ertiary interactions in determining the uniqueness of the native state , as well as the cooperativity of the folding process. Thus, these sim ulations may provide guidelines for the early stages of the protein de sign process. Possible applications to the general protein folding pro blem are also briefly discussed. (C) 1995 American Institute of Physic s.