Packing regularities in folded proteins

Abstract

Using lattice models of proteins is a common method to reduce conformational space. Despite the suitability of various lattice geometries, the optimal packing geometry of residues in folded structures, or the generic preference for regular packing, if any, remains unclear. In this thesis, a degree of intrinsic regularity in residue packing is revealed upon optimal superimposition of clusters of residues from Protein Data Bank structures. This regularity can be identified as an incomplete distorted face-centered cubic packing, i.e. the closest packing of identical spheres, emerging when the tertiary structure is observed at a coarse-grained (single-site-per-residue) scale. It is apparently favored by the drive for maximizing packing density, and shows little variation with specific amino acid type. Both the extreme cases of solvent-exposed and completely buried residue neighborhoods approximate this generic packing, their only difference being in the number (and not the type) of coordination sites that are occupied (or left void for solvent occupancy). Interestingly, these sites are not staggered even for the solvent-exposed residues on the surface and it is concluded that all residues, even those at the protein surface are densely packed. The packing density is approximately uniform when the volume of solvent surrounding the residues is excluded.