Hydrogen Bond Dynamics of Histamine Monocation in Aqueous Solution: Car–Parrinello Molecular Dynamics and Vibrational Spectroscopy Study

Abstract

Hydration of histamine was examined by infrared spectroscopy and Car-Parrinello molecular dynamics simulation. Histamine is a neurotransmitter and inflammation mediator, which at physiological pH conditions is present mainly in monocationic form. Our focus was on the part of vibrational spectra that corresponds to histamine N-H stretching, since these degrees of freedom are essential for its interactions with either water molecules or transporters and receptors. Assignment of the experimental spectra revealed a broad feature between 3350 and 2300 cm(-1), being centered at 2950 cm(-1), which includes a mixed contribution from the ring N-H and the aminoethyl N-H stretching vibrations. Computational analysis was performed in two ways: first, by making Fourier transformation on the autocorrelation function of all four N-H bond distances recorded during CPMD run, and second, and most importantly, by incorporating quantum effects through applying an a posteriori quantization of all N-H stretching motions utilizing our snapshot analysis of the fluctuating proton potential. The one-dimensional vibrational Schrödinger equation was solved numerically for each snapshot, and the N-H stretching envelopes were calculated as a superposition of the 0→1 transitions. The agreement with the experiment was much better in the case of the second approach. Our calculations clearly demonstrated that the ring amino group absorbs at higher frequencies than the remaining three amino N-H protons of the protonated aminoethyl group, implying that the chemical bonding in the former group is stronger than in the three amino N-H bonds, thus forming weaker hydrogen bonding with the surrounding solvent molecules. In this way the results of the simulation complemented the experimental spectrum that cannot distinguish between the two sets of protons. The effects of deuteration were also considered. The resulting N-D absorption is narrower and red-shifted. The presented methodology is of general applicability to strongly correlated systems, and it is particularly tuned to provide computational support to vibrational spectroscopy. Perspectives are given for its future applications in computational studies of tunneling in enzyme reactive centers and for receptor activation.

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

“…[108][109][110][111][112] Following discovery of water molecules durably located and proximate to sulfur, we began extensive CP-MD simulations to investigate the organization of water molecules around dissolved cysteine. 113 Preliminary low-temperature in silico experiments have produced H-bonding networks that include stabilized water molecules positionally compatible with the MXAN fit.…”

Assembly and stability of Salmonella enterica ser. Typhi TolC protein in POPE and DMPE

“…Vibrational spectroscopy techniques such as infrared spectroscopy have been applied to study the hydration of small molecules [68]. Hydrogen bonding studies using simulation and vibrational spectroscopy between membrane lipids and the protein [69,70] and also the lipid headgroups with water [71,72] showed that lipids not only provide a hydrophobic environment for membrane protein folding but also form hydrogen bonds with protein residues, which stabilize it within the membrane.…”

Hydrogen Bond Dynamics of Histamine Monocation in Aqueous Solu-tion: How Geometric Parameters Influence the Hydrogen Bond Strength

“…The approach involved the construction of one dimensional proton potentials on snapshot structures extracted from a CPMD trajectory, followed by solving the one-dimensional vibrational Schroedinger equation. By separating the amino N-H vibrations of the protonated ethylamino chain from those within the imidazole ring in the experimental spectra, we clearly demonstrated that the former moiety forms stronger hydrogen bonds with the surrounding water molecules, 9,10 which should be significant for the biological function of histamine. It remains a challenge to identify how the fluctuating intra-and intermolecular geometric parameters influence the N-H stretching frequencies, which is the aim of the present work.…”

“…The latter is in line with recent molecular dynamics simulations by Keserű and co-workers 7 that emphasized the role of water-histamine interactions at the binding site of the human histamine H4 receptor, being in agreement with several previous reports. 8 Recently, we modeled the nature of the hydration of physiological histamine monocation by using CarParrinello molecular dynamics simulations (CPMD) 9 and a static cluster model. 10 In the former study, we simulated the N-H stretching band envelope, which are degrees of freedom that predominantly influence the strength of the hydrogen bonding as probed by the vibrational spectroscopy.…”

“…This approach was previously used in the case of a very strong hydrogen bonding in the crystals of sodium hydrogen bis(sulfate), 13,14 where, remarkably, no appreciable correlation between the instantaneous geometric parameters and the pertinent OH stretching frequency could be found, demonstrating the extreme complexity of the short and strong hydrogen bond. In contrast, aqueous histamine forms relatively long and weak hydrogen bonds with water; 9,10 hence part of the motivation for the present study is a comparison of the geometry-frequency correlation patterns between strong and weak hydrogen bonds.…”