(708g) Modifying Nonplanar Vibrational Modes of Aromatic Rings in Biomolecular Modeling

Several biomolecular studies have stated the important role of aromatic amino acids such as Tryptophan (TRP) and Tyrosine (TYR) in the folding process of proteins at water-membrane interfaces. The accuracy of biomolecular modeling results is based in part on force field (FF) parameters. In this study, molecular dynamics (MD) simulations were conducted on TRP and TYR amino acids in solution by applying the most recent version of Charmm 36. The results from these simulations show that the structures of aromatic rings have deviations from planarity. Considering improper torsion in MD simulation brings the aromatic rings in TYR and TRP closer to planar structures. On the other hand, inherent vibrations of atoms in molecules might be the reason for this nonplanarity. Hence, a concern arises about the effects of imposing improper torsion parameters on the nonplanar vibrational modes of atoms in the aromatic ring. Addressing this concern requires calculating these vibrational modes on the basis of FFs and comparing these obtained vibrational modes to experimental data. All-atom Normal Mode Analysis (NMA) provides the vibrational frequencies of those rings on the basis of diverse FFs. Analytical and numerical NMA were applied on the configuration results of MD simulations to calculate the average nonplanar vibrational frequencies and normal modes of atoms in those rings. The results of NMA were compared to Raman spectra and to results of quantum calculations for TRP and TYR. The nonplanar mode frequencies that are obtained for both TRP and TYR on the basis of the standard Charmm36 are higher compared to Raman spectra and to the results of quantum calculations. These frequencies increase even more when improper torsions are added to Charmm36. Increasing the improper torsion force constants in the potential equation shifts these frequencies to even higher amounts. Beside the improper torsions, torsion angles that include atoms in the ring have a direct effect on nonplanar motion. In order to obtain proper nonplanar frequencies, NMA has been applied on different sets of amended torsion angle parameters with and without considering improper torsion angles. The results of these calculations demonstrate that by applying a specific set of amended torsion angle parameters and considering the improper torsion with specific force constants, the pattern and frequencies of nonplanar normal modes can match properly with Raman spectra and the results of quantum calculations.