Probing micro-solvation in “numbers”: the case of neutral dipeptides in water

Abstract

How many solvent molecules and in what way do they interact directly with biomolecules? This is one of the most challenging questions regarding a deep understanding of biomolecular functionalism and solvation. We herein present a novel NMR spectroscopic study, achieving for the first time the quantification of the directly interacting water molecules with several neutral dipeptides. Our proposed method is supported by both molecular dynamics simulations and density functional theory calculations, advanced analysis of which allowed the identification of the direct interactions between solute-solvent molecules in the zwitterionic L-alanyl-L-alanine dipeptide-water system. Beyond the quantification of dipeptide-water molecule direct interactions, this NMR technique could be useful for the determination and elucidation of small to moderate bio-organic molecular groups' direct interactions with various polar solvent molecules, shedding light on the biomolecular micro-solvation processes and behaviour in various solvents.

Quantum Mechanics Approach to Hydration Energies and Structures of Alanine and Dialanine

“…The number of water molecules directly bonded to dialanine is ten for both cation and zwitterion (with the exception of Ala 2 ⋅ 18 H 2 O_PPII_C). This is in agreement with recent NMR measurements of the 13 C α and 13 C β longitudinal relaxation times of several dipeptide zwitterions at three different magnetic fields, which allowed quantification of the strongly and directly interacting water molecules (8±1) …”

“…[9][10][11][12] From the experimental point of view,t here is no exhaustive experimental technique that directly probess pecific biomolecule-water interactions in solution, sincec hanges in geometricala rrangement are too fast, on the picosecondt imescale. [13] Nevertheless, neutron scattering, [14] NMR, [15,16] terahertz, [17][18][19] dielectric relaxation, [20] and fluorescence [21] spectroscopy has shownt hat molecular reorientation occurs more slowly than in bulk water,m ainly because of the peptide-water H-bonds and the topologically het-erogeneous nature of ap eptide surface, which disrupts the synergistic water-water reorientation mechanisms.…”

Interfacial water at the trialanine hydrophilic surface: a DFT electronic structure and bottom-up investigation

“…[5][6][7][8][9][10][11][12]21 The formation of strong H-bonds, which disrupts the water structure and avoids synergistic water molecule reorientation in the immediate vicinity of the peptide, is responsible for the slowdown of water motion. [5][6][7][8][9][10][11][12]21 The formation of strong H-bonds, which disrupts the water structure and avoids synergistic water molecule reorientation in the immediate vicinity of the peptide, is responsible for the slowdown of water motion.…”

Highly Efficient and Chemoselective Zinc‐Catalyzed Hydrosilylation of Esters under Mild Conditions

“…They are ideal biomolecules to probe the complex nature of the peptide–water interface through various spectroscopic methods. For some of these molecules, water 2 H NMR and 17 O NMR spin relaxation5, 6 and quasielastic neutron scattering (QENS)7, 8 report a slowdown peptide hydration shell by a factor of about 2, whereas related molecular dynamics calculations suggest the involvement of 30–50 water molecules depending on the considered amino acid. QENS experiments also give an indication that a few water molecules are also strongly slowed down.…”