Energetics, structures, vibrational frequencies, vibrational absorption, vibrationalcircular 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 usingthe Becke 3LYP hybrid functional and the 6-31G*basis set. The structures, conformational energies, vibrational frequencies, vibrationalabsorption (VA) intensities, vibrational circular dichroism (VCD) intensities andRaman scattering intensities are reported for the conformers of LeuE which areexpected to be populated at room temperature. The species of LeuE present innon-polar solvents is the neutral non-ionic species with the NH2 andCO2Hgroups, in contrast to the zwitterionic neutral species with the NH3+ andCO2−groups which predominates in aqueous solution and in the crystal. All of ourattempts to find the zwitterionic species in the isolated state failed, with theresult that a hydrogen atom from the positively charged N-terminus ammoniumgroup transferred either to one of the oxygens of the carboxylate group of theC-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 theisolated state. Spectral simulations of the species expected to be found in theisolated state can be compared to the measured VA, VCD and Raman spectra ofLeuE in non-polar solvents to identify which conformer or conformers of LeuE arepresent in these media. Characteristic features in the VCD spectra are moresensitive to conformational changes than those in either the VA or Ramanspectra, similar to the characteristic features in electronic circular dichroismspectra with respect to those in the UV–vis electronic absorption spectra. Finally,we have also attempted to stabilize the zwitterionic species by treatingthe aqueous environment by using a continuum solvent approach, theOnsager model. Here we found that the zwitterionic species is now stable.The neutral species in an aqueous environment was also modelled by thecontinuum solvent approaches to determine the relative stability of these twospecies in this new aqueous environment. Here the relative energy of thezwitterionic species is higher than neutral species, in contradiction toexperiment. Hence the use of explicit water molecules plus either this or anothercontinuum model to treat the bulk water environment is necessary tomake the zwitterionic species more stable than the neutral species. We arepursuing explicit water molecules to treat LeuE in this environment.