A novel approach has been taken to the problem of protein folding that examines the complete range of folded topologies accessible in the compact state of globular proteins. The procedure is to generate all conformations, with volume exclusion, upon a lattice in a space restricted to the individual protein's known compact conformational space. The importance of knowing with certainty the range of viable protein conformations is a compelling issue. The present studies have aimed at a more thorough evaluation of protein folds, with less than atomic detail. The concept that the overall chain tracing is more important than the precise positioning of each atom has been the basic assumption. Such atomless structures can be evaluated with potential function that are basically pairwise residue-residue hydrophobicities. Other aspects being considered include: folding intermediates, combining the folding calculations with sequence homologies and investigating hydrophobic cores, binding, choices of overall shapes and the relationship between good packing and secondary structures. The residue potentials are being generalized for application to situations with different solvent conditions.
