Interaction Analysis of the Native Structure of Prion Protein with Quantum Chemical Calculations

We examined the solvent interaction and intramolecular interaction of the native structure of prion protein (PrP) using quantum chemical calculations based on the fragment molecular orbital (FMO) method. The influence due to the geometrical fluctuation was taken into account by performing calculations on forty different conformations. Each FMO calculation was carried out at the MP2 level of theory with the cc-pVDZ in which the resolution of the identity approximation was employed to reduce the computational cost. The solvent interaction energies obtained from the calculations provided information about the hydrophilicity of the three α-helices. We examined the roles of the charged residues in retaining the native structure of PrP with the calculated intramolecular interaction energies. The analysis, focused on van der Waals interaction, showed that the hydrophobic residues were important for the stability of the native structure. Our results were also discussed in relation to the identified pathogenetic mutations of prion diseases. Additionally, we examined the distribution of the calculated values with 40 structures, in which we demonstrated the influence of geometrical fluctuations on quantum chemical calculations.