Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes.

We assume that each class of protein has a core structure that is defined by internal residues, and that the external, solvent-contacting residues contribute to the stability of the structure, are of primary importance to function, but do not determine the architecture of the core portions of the polypeptide chain. An algorithm has been developed to supply a list of permitted sequences of internal residues compatible with a known core structure. This list is referred to as the tertiary template for that structure. In general the positions in the template are not sequentially adjacent and are distributed throughout the polypeptide chain. The template is derived using the fixed positions for the main-chain and beta-carbon atoms in the test structure and selected stereochemical rules. The focus of this paper is on the use of two packing criteria: avoidance of steric overlap and complete filling of available space. The program also notes potential polar group interactions and disulfide bonds as well as possible burial of formal charges. Central to the algorithm is the side-chain rotamer library. In an update of earlier studies by others, we show that 17 of the 20 amino acids (omitting Met, Lys and Arg) can be represented adequately by 67 side-chain rotamers. A list of chi angles and their standard deviations is given. The newer, high-resolution, refined structures in the Brookhaven Protein Data Bank show similar mean chi values, but have much smaller deviations than those of earlier studies. This suggests that a rotamer library may be a better structural approximation than was previously thought. In using packing constraints, it has been found essential to include all hydrogen atoms specifically. The "unified atom" representation is not adequate. The permitted rotamer sequences are severely restricted by the main-chain plus beta-carbon atoms of the test structure. Further restriction is introduced if the full set of atoms of the external residues are held fixed, the full-chain model. The space-filling requirement has a major role in restricting the template lists. The preliminary tests reported here make it appear likely that templates prepared from the currently known core structures will be able to discriminate between these structures. The templates should thus be useful in deciding whether a sequence of unknown tertiary structure fits any of the known core classes and, if a fit is found, how the sequence should be aligned in three dimensions to fit the core of that class.(ABSTRACT TRUNCATED AT 400 WORDS)