Water interaction differences determine the relative energetic stability of the polyproline II conformation of the alanine dipeptide in aqueous environments

Abstract

Although subsequent studies have provided extensive support for the 1968 Tiffany and Krimm proposal (Biopolymers 6, 1379) that the polyproline II (PPII) conformation is a significant component of the structure of unordered polypeptide chains, two issues are still not fully resolved: the PPII persistence length in a chain and the source of its relative stability with respect to the β-conformation. We examine the latter question by studying the B97-D/6-31++G(**) energy, in the absence and presence of a reaction field, of the alanine dipeptide hydrated by various amounts of explicit waters and resolving this into its three components: the energies of the individual solvated peptides and water structures plus the interaction energy involving them. We find that the relative stability of the PPII conformation is determined mainly by the difference in the interaction energies of the water structures in the near-peptide layers.

The amide III vibrational circular dichroism band as a probe to detect conformational preferences of alanine dipeptide in water

“…The most favorable structure of ADP in P II conformation with six water molecules, shown in Figure , has both the CO and NH backbone groups connected with water bridges that stabilize this conformation. Thus, the P II structure fully utilizes the hydrogen bonding capacity of the CO and NH groups, maximizes peptide–water cooperativity, and leaves the first solvation layer of hydration able to participate in further hydrogen bonding with the next solvation shell . This pattern is observed with all other structures representing the ensemble of P II conformation.…”

“…Initially, we construct three different conformations of ADP, P II , β, and α R , which can typically be observed in aqueous solution, by applying dihedral angles constraints. To account for the proper treatment of solvation, the use of only continuum dielectric model was refined by inclusion of explicit water molecules as suggested before by several authors . However, the number of explicit water molecules per ADP and their initial positions are not known a priori .…”

“…Blocked alanine dipeptide (ADP), Ac‐Ala‐NHMe, provides a good model molecule to study intrinsic conformational preferences of alanine residue and to further determine the impact of the solvent on the dihedral angles populations. Structural implications of ADP vibrational spectra have been studied extensively in the past both experimentally and theoretically . Infrared (IR) and Raman study of conformational population of ADP in water have shown high polyproline II (P II ) population (60%), followed by β conformation (29%) and right handed α R conformation (11%) .…”

“…Structural implications of ADP vibrational spectra have been studied extensively in the past both experimentally [3][4][5] and theoretically. [6][7][8] Infrared (IR) and Raman study of conformational population of ADP in water have shown high polyproline II (P II ) population (60%), followed by b conformation (29%) and right handed a R conformation (11%). 5 Several studies based on the density functional theory (DFT) support the prediction of high level of P II conformation of ADP given that some of the water molecules are explicitly present in the calculation.…”

“…5 Several studies based on the density functional theory (DFT) support the prediction of high level of P II conformation of ADP given that some of the water molecules are explicitly present in the calculation. [7][8][9][10][11] The explicit water molecules interact with the CO and NH groups of peptide backbone by formation of hydrogen bonds that subsequently stabilize the conformations.…”