FORCES OF TERTIARY STRUCTURAL ORGANIZATION IN GLOBULAR-PROTEINS

The tertiary structures of globular proteins have remarkable and compl ex symmetries. What forces cause them? We find that a very simple mode l reproduces some of those symmetries. Proteins are modeled as copolym ers of specific sequences of hydrophobic (H) and polar (P) monomers (H P model) configured as self-avoiding flights on simple three-dimension al cubic lattices. The model has no parameters; we just seek the confo rmations that have the global maximum number of HH contacts for any gi ven sequence. Finding global optima for chains in this model has not b een computationally possible before for chains longer than 36-mers. We report here a procedure that can find all the globally optimal confor mations, the number of which defines the degeneracy of a sequence, for chains up to 88 monomers long. It is about 37 orders of magnitude fas ter than previous exact methods. We find that degeneracy is an importa nt aspect of sequence design. So far, we have found that four-helix bu ndles, alpha/beta-barrels, and parallel beta-helices are globally opti mal conformations of polar/nonpolar sequences that have minimal degene racy.