Ramachandran backbone potential energy surfaces of aspartic acid and aspartate residues: implications on allosteric sites in receptor–ligand complexations

Abstract

Ramachandran backbone potential energy surfaces (PES) were generated for N-acetyl- l-aspartic acid- N′-methylamide and N-acetyl- l-aspartate- N′-methylamide. Relatively few minima were observed from the Ramachandran PES of the aspartate ion while many existed for both endo and exo forms of the aspartic acid residue. By comparing the relative stabilization energies as well as the vertical and adiabetic proton affinities of the two forms the aspartic acid residue, it was previously determined that aspartic acid may rather change its backbone conformation before deprotonation into the aspartate ion. Taken together, many stable conformers may exist for both endo and exo forms of aspartic acid but when deprotonated they lead to the same aspartate ion which has remarkably few conformations. This feature may have significant biological implications, and a receptor–ligand complexation model is proposed where aspartate and aspartic acid could represent, respectively, resting and active states of a putative binding site in a hypothetical protein. More importantly, however, the aspartyl residues may represent important allosteric sites for regulatory ions, directly modulating the specificity of ligand docking in a receptor protein and affecting downstream biological mechanisms.