Anharmonic Vibrational Analysis of Biomolecules and Solvated Molecules Using Hybrid QM/MM Computations

Abstract

Quantum mechanics/molecular mechanics (QM/MM) calculations are applied for anharmonic vibrational analyses of biomolecules and solvated molecules. The QM/MM method is implemented into a molecular dynamics (MD) program, GENESIS, by interfacing with external electronic structure programs. Following the geometry optimization and the harmonic normal-mode analysis based on a partial Hessian, the anharmonic potential energy surface (PES) is generated from QM/MM energies and gradients calculated at grid points. The PES is used for vibrational self-consistent field (VSCF) and post-VSCF calculations to compute the vibrational spectrum. The method is first applied to a phosphate ion in solution. With both the ion and neighboring water molecules taken as a QM region, IR spectra of representative hydration structures are calculated by the second-order vibrational quasi-degenerate perturbation theory (VQDPT2) at the level of B3LYP/cc-pVTZ and TIP3P force field. A weight-average of IR spectra over the structures reproduces the experimental spectrum with a mean absolute deviation of 16 cm –1 . Then, the method is applied to an enzyme, P450 nitric oxide reductase (P450nor), with the NO molecule bound to a ferric (Fe III ) heme. Starting from snapshot structures obtained from MD simulations of P450nor in solution, QM/MM calculations have been carried out at the level of B3LYP-D3/def2-SVP(D). The spin state of Fe III (NO) is likely a closed-shell singlet state based on a ratio of N–O and Fe–NO stretching frequencies (ν N–O and ν Fe–NO ) calculated for closed- and open-shell singlet states. The calculated ν N–O and ν Fe–NO overestimate the experimental ones by 120 and 75 cm –1 , respectively. The electronic structure and solvation of Fe III (NO) affect the structure around the heme of P450nor leading to an increase in ν N–O and ν Fe–NO .

Spectra–Structure Correlations in Isotopomers of Ethanol (CX3CX2OX; X = H, D): Combined Near-Infrared and Anharmonic Computational Study

“…Recently, a number of theoretical reconstructions of NIR spectra by means of efficient vibrational second-order perturbation (VPT2) method have been reported [18]; e.g., carboxylic acids [19], fatty acids [20,21,22], aminoacids [23], nucleobases [24], nitriles [25], azines [26], phenols [27,28], and alcohols [29,30]. Considerable efforts have been undertaken in order to develop anharmonic approaches applicable to even larger molecular systems [31,32,33,34]. On the other hand, meticulous probing of vibrational potential capable of yielding nearly-exact results is also available [35,36,37,38].…”

Tailored multilevel approaches in vibrational structure theory: A route to quantum mechanical vibrational spectra for complex systems

“…Such applications of vibrational structure theory usually use vibrational coordinates obtained in a partial Hessian analysis of the active system. [42,43,44,45] This setup has, in an impressive manner, been combined with multiscale schemes for electronic energy calculations in the generation of the potential energy surface. [43,44,45] Compared to this partial Hessian approach, the FALCON scheme, however, provides purely vibrational coordinates, without spurious contribution of translational and rotational degrees of freedom.…”

“…Its generation is not in the scope of the present perspective, but a few comments are appropriate: The challenges of generating the potential energy surface increase tremendously with system size. However, its generation can benefit from similar approaches as described above: This includes adaptively choosing the MCR of the typically applied n-mode expansion [46,16,40] , as well as similar multiscale [43,44,45] and fragmentation [41,6,45] ideas for the underlying electronic energy points. Another critical challenge is the treatment of rather flexible structures with a large manifold of local minima on the potential energy surface.…”

“…The final result is then obtained via weight averaging of these vibrational spectra. [1,45,47,48] This approach has, for instance, been applied in vibrational structure calculations on polyamides examples [1,48] in reduced vibrational space. These figure).…”

Combining Quantum Mechanics and Machine-Learning Calculations for Anharmonic Corrections to Vibrational Frequencies

“…To obtain additional progress in computational spectroscopy, the current challenge is to carry out calculations for large molecules while maintaining the accuracy obtained for the smaller ones [14][15][16][17][18][19]. Such glass ceiling proves to be even more difficult to break when it comes to computing the anharmonic corrections to vibrational frequencies [14][15][16][17][18][19].…”