Energetics, structures, vibrational frequencies, vibrational absorption, vibrational circular dichroism and Raman intensities of Leu-enkephalin

Abstract

Here we present several low energy conformers of Leu-enkephalin (LeuE) calculated with the density functional theory using the Becke 3LYP hybrid functional and the 6-31G* basis set. The structures, conformational energies, vibrational frequencies, vibrational absorption (VA) intensities, vibrational circular dichroism (VCD) intensities and Raman scattering intensities are reported for the conformers of LeuE which are expected to be populated at room temperature. The species of LeuE present in non-polar solvents is the neutral non-ionic species with the NH2 and CO2H groups, in contrast to the zwitterionic neutral species with the NH3+ and CO2− groups which predominates in aqueous solution and in the crystal. All of our attempts to find the zwitterionic species in the isolated state failed, with the result that a hydrogen atom from the positively charged N-terminus ammonium group transferred either to one of the oxygens of the carboxylate group of the C-terminus or to the oxygen of the amide group of one of the other residues. Hence we conclude that the zwitterionic species of LeuE is not stable in the isolated state. Spectral simulations of the species expected to be found in the isolated state can be compared to the measured VA, VCD and Raman spectra of LeuE in non-polar solvents to identify which conformer or conformers of LeuE are present in these media. Characteristic features in the VCD spectra are more sensitive to conformational changes than those in either the VA or Raman spectra, similar to the characteristic features in electronic circular dichroism spectra with respect to those in the UV–vis electronic absorption spectra. Finally, we have also attempted to stabilize the zwitterionic species by treating the aqueous environment by using a continuum solvent approach, the Onsager model. Here we found that the zwitterionic species is now stable. The neutral species in an aqueous environment was also modelled by the continuum solvent approaches to determine the relative stability of these two species in this new aqueous environment. Here the relative energy of the zwitterionic species is higher than neutral species, in contradiction to experiment. Hence the use of explicit water molecules plus either this or another continuum model to treat the bulk water environment is necessary to make the zwitterionic species more stable than the neutral species. We are pursuing explicit water molecules to treat LeuE in this environment.

Surface-enhanced Raman scattering and adsorption studies of morphine on silver island film

“…The assignment of the normal vibrational modes for the molecule was accomplished mainly by the wavenumbers and intensities as obtained by the B3LYP method and by comparison with related molecules like enkephalin [22]. The theoretical results obtained at the 6-31G(d) level reproduce closest the experimental values, though there are 5-15 cm À1 shifts for some peaks.…”

Interactions of Tyrosine in Leu-Enkephalin at a Membrane−Water Interface: An Ultrafast Two-Dimensional Infrared Study Combined with Density Functional Calculations and Molecular Dynamics Simulations

“…28 To investigate the conformational dependence of Tyr ring mode frequencies, DFT calculations were carried out on six representative conformations of neutral Lenk in the gas phase at the B3LYP/6-31G(d) level. The starting conformations were obtained from a previous study 50 and optimized before performing vibrational frequency analyses. The calculated results were scaled by a factor of 0.968 to make the Tyr ring mode frequencies close to the experimental FT IR peak positions.…”

Mixing parameters for geometry optimization using the Hamiltonian algorithm

“…Recently, the multiple minimum problems of biomolecules in complex environments were extensively studied [25][26][27][28][29][30][31][32][33][34][35][36]. In order to show an example of the optimization of more realistic system than a butane molecule and the possibility of the application of the HA optimization on the biomolecule, the optimized HSD structures of N-acetyl L-histidine N'-Methyl amide (NALHNMA), that was reported by Jalkannen et al [32], are calculated by using the HA.…”