Ramachandran Revisited. DFT Energy Surfaces of Diastereomeric Trialanine Peptides in the Gas Phase and Aqueous Solution

We report DFT calculations at the B3LYP/D95(d,p) level on the gas phase, aqueous solvation and solvated energies as functions of the central ψ and ϕ dihedral angles (in steps of 5° each) of acetyl-LAla-LAla-LAla-NH2 (3AL) and its diastereomer, acetyl-LAla-DAla-LAla-NH2 (3AD). In addition to structures without internal H-bonds (C5 interactions are neglected), many (95) structures containing internal H-bonds were completely optimized. The only minima for non-H-bonding structures in the gas phase correspond to extended β-strands for both diastereomers. Some (but not all) structures with internal H-bonds are more stable than those without them. The energy landscapes for the solvated species show multiple minima for the non-H-bonding species and a single minimum for the H-bonding species (310-helix), suggesting that the equilibrium conformational mixture in water be composed of the extended β-strand, polyproline II, 310-helix, and α-helix-like (with no H-bonds) conformations which are all within about 1 kcal/m...