Implications of N and C-Terminal Proximity for Protein Folding

We have investigated the proximity of the N and C termini in protein structures, and developed a model to test the theoretical possibility that proteins fold with their termini closely associated. On average, the distance between the termini is not significantly different from what would be expected based on chance. However, the theoretical model indicated that it is possible to greatly decrease the N-to-C terminal distance by allowing small (approximately six amino acid residues) solvent-accessible terminal fragments to move. Subsequent to this distance minimization method, more than 90% of the proteins studied had smaller-than-expected N-to-C distances, but only minor structural modification.