Carbonyl-carbonyl interactions stabilize the partially allowed Ramachandran conformations of asparagine and aspartic acid

Asparagine and aspartate are known to adopt conformations in the left-hande d alpha-helical region and other partially allowed regions of the Ramachand ran plot more readily than any other non-glycyl amino acids. The reason for this preference has not been established. An examination of the local envi ronments of asparagine and aspartic acid in protein structures with a resol ution better than 1.5 Angstrom revealed that their side-chain carbonyls are frequently within 4 Angstrom of their own backbone carbonyl or the backbon e carbonyl of the previous residue. Calculations using protein structures w ith a resolution better than 1.8 Angstrom reveal that this close contact oc curs in more than 80% of cases. This carbonyl-carbonyl interaction offers a n energetic sabilization for the partially allowed conformations of asparag ine and aspartic acid with respect to all other non-glycyl amino acids. The non-covalent attractive interactions between the dipoles of two carbonyls has recently been calculated to have an energy comparable to that of a hydr ogen bond. The preponderance of asparagine in the left-handed alpha-helical region, and in general of aspartic acid and asparagine in the partially al lowed regions of the Ramachandran plot. may be a consequence of this carbon yl-carbonyl stacking interaction.