Simulations of liquid ammonia based on the combined quantum mechanical/molecular mechanical (QM/MM) approach

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely, HF/MM and B3LYP/MM, have been performed to investigate the local structure and dynamics of liquid ammonia. The most interesting region, a sphere containing a central reference molecule and all its nearest surrounding molecules (first coordination shell), was treated by the Hartree-Fock (HF) and hybrid density functional B3LYP methods, whereas the rest of the system was described by the classical pair potentials. On the basis of both HF and B3LYP methods, it is observed that the hydrogen bonding in this peculiar liquid is weak. The structure and dynamics of this liquid are suggested to be determined by the steric packing effects, rather than by the directional hydrogen bonding interactions. Compared to previous empirical as well as Car-Parrinello (CP) molecular dynamics studies, our QM/MM simulations provide detailed information that is in better agreement with experimental data.     

Cu(II) in liquid ammonia: an approach by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulation.

To investigate the solvation structure of the Cu(II) ion in liquid ammonia, ab initio quantum-mechanical/molecular-mechanical (QM/MM) molecular dynamics (MD) simulations were carried out at Hartree Fock (HF) and hybrid density functional theory (B3 LYP) levels. A sixfold-coordinated species was found to be predominant in the HF case whereas five- and sixfold-coordinated complexes were obtained in a ratio 2:1 from the B3 LYP simulation. In contrast to hydrated Cu(II), which exhibits a typical Jahn-Teller distortion, the geometrical arrangement of ligand molecules in the case of ammonia can be described as a [2 + 4] ([2 + 3]) configuration with 4 (3) elongated copper-nitrogen bonds. First shell solvent exchange reactions at picosecond rate took place in both HF and B3 LYP simulations, again in contrast to the more stable sixfold-coordinated hydrate. NH3 ligands apparently lead to strongly accelerated dynamics of the Cu(II) solvate due to the "inverse" [2 + 4] structure with its larger number of elongated copper-ligand bonds. Several dynamical properties, such as mean ligand residence times or ion-ligand stretching frequencies, prove the high lability of the solvated complex.     

A combined QM/MM molecular dynamics simulations study of nitrate anion (NO3-) in aqueous solution

The structural and dynamical properties of NO3- in dilute aqueous solution have been investigated by means of two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely HF/MM and B3LYP/MM, in which the ion and its surrounding water molecules were treated at HF and B3LYP levels of accuracy, respectively, using the DZV+ basis set. On the basis of both HF and B3LYP methods, a well-defined first hydration shell of NO3- is obtainable, but the shell is quite flexible and the hydrogen-bond interactions between NO3- and water are rather weak. With respect to the detailed analysis of the geometrical arrangement and vibrations of NO3-, the experimentally observed solvent-induced symmetry breaking of the ion is well reflected. In addition, the dynamical information, i.e., the bond distortions and shifts in the corresponding bending and stretching frequencies as well as the mean residence time of water molecules surrounding the NO3- ion, clearly indicates the "structure-breaking" ability of this ion in aqueous solution. From a methodical point of view it seems that both the HF and B3LYP methods are not too different in describing this hydrated ion by means of a QM/MM simulation. However, the detailed analysis of the dynamics properties indicates a better suitability of the HF method compared to the B3LYP-DFT approach.     

Characteristics of CO3(2-)-water hydrogen bonds in aqueous solution: insights from HF/MM and B3LYP/MM MD simulations

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, namely HF/MM and B3LYP/MM, have been performed to investigate the local hydration structure and dynamics of carbonate (CO(3)(2-)) in dilute aqueous solution. With respect to the QM/MM scheme, the QM region, which contains the CO(3)(2-) and its surrounding water molecules, was treated at HF and B3LYP levels of accuracy, respectively, using the DZV+ basis set, while the rest of the system is described by classical MM potentials. For both the HF/MM and B3LYP/MM simulations, it is observed that the hydrogen bonds between CO(3)(2-) oxygens and their nearest-neighbor waters are relatively strong, i.e., compared to water-water hydrogen bonds in the bulk, and that the first shell of each CO(3)(2-) oxygen atom somewhat overlaps with the others, which allows migration of water molecules among the coordinating sites to exist. In addition, it is observed that first-shell waters are either "loosely" or "tightly" bound to the respective CO(3)(2-) oxygen atoms, leading to large fluctuations in the number of first-shell waters, ranging from 1 to 6 (HF/MM) and 2 to 7 (B3LYP/MM), with the prevalent value of 3. Upon comparing the HF and B3LYP methods in describing this hydrated ion, the latter is found to overestimate the hydrogen-bond strength in the CO(3)(2-)-water complexes, resulting in a slightly more compact hydration structure at each of the CO(3)(2-) oxygens.     

Correlation effects on the structure and dynamics of the H3O+ hydrate: B3LYP/MM and MP2/MM MD simulations

Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations, namely B3LYP/MM and MP2/MM, have been performed to investigate the possible influence of electron correlation on the structure and dynamics of the H(3)O(+) hydrate. In comparison to the previously published HF/MM results, both B3LYP/MM and MP2/MM simulations clearly reveal stronger H(3)O(+)-water hydrogen bond interactions, which are reflected in a slightly greater compactness of the H(3)O(+) hydrate. However, the B3LYP/MM simulation, although providing structural details very close to the MP2/MM data, shows an artificially slow dynamic nature of some first shell water molecules as a consequence of the formation of a long-lived H(3)O(+)···H(2)O hydrogen bonding structure.     

Structure and dynamics of hydrated NH(4) (+): an ab initio QM/MM molecular dynamics simulation

A combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation has been performed to investigate solvation structure and dynamics of NH(4) (+) in water. The most interesting region, the sphere includes an ammonium ion and its first hydration shell, was treated at the Hartree-Fock level using DZV basis set, while the rest of the system was described by classical pair potentials. On the basis of detailed QM/MM simulation results, the solvation structure of NH(4) (+) is rather flexible, in which many water molecules are cooperatively involved in the solvation shell of the ion. Of particular interest, the QM/MM results show fast translation and rotation of NH(4) (+) in water. This phenomenon has resulted from multiple coordination, which drives the NH(4) (+) to translate and rotate quite freely within its surrounding water molecules. In addition, a "structure-breaking" behavior of the NH(4) (+) is well reflected by the detailed analysis on the water exchange process and the mean residence times of water molecules surrounding the ion.     

Ab initio QM/MM dynamics of H3O+ in water

A molecular dynamics (MD) simulation based on a combined ab initio quantum mechanics/molecular mechanics (QM/MM) method has been performed to investigate the solvation structure and dynamics of H3O+ in water. The QM region is a sphere around the central H3O+ ion, and contains about 6-8 water molecules. It is treated at the Hartree-Fock (HF) level, while the rest of the system is described by means of classical pair potentials. The Eigen complex (H9O4+) is found to be the most prevalent species in the aqueous solution, partly due to the selection scheme of the center of the QM region. The QM/MM results show that the Eigen complex frequently converts back and forth into the Zundel (H5O2+) structure. Besides the three nearest-neighbor water molecules directly hydrogen-bonded to H3O+, other neighbor waters, such as a fourth water molecule which interacts preferentially with the oxygen atom of the hydronium ion, are found occasionally near the ion. Analyses of the water exchange processes and the mean residence times of water molecules in the ion's hydration shell indicate that such next-nearest neighbor water molecules participate in the rearrangement of the hydrogen bond network during fluctuative formation of the Zundel ion and, thus, contribute to the Grotthuss transport of the proton.     

Theoretical Study on Co^3＋ in Aqueous Solution in Terms of ABEEM/MM Model

A detailed theoretical investigation on Co^3＋ hydration in aqueous solution has been carded out by means of molecular dynamics （MD） simulations based on the atom-bond electronegativity equalization method fused into molecular mechanics （ABEEM/MM）. The effective Co^3＋ ion-water potential has been constructed by fitting to ab initio structures and binding energies for ionic clusters. And then the ion-water interaction potential was applied in combination with the ABEEM-7P water model to molecular dynamics simulations of single Co^3＋（aq.） solution, managing to reproduce many experimental structural and dynamical properties of the solution. Here, not only the common properties （radial distribution function, angular distribution function and solvation energy） obtained for Co^3＋ in ABEEM-7P water solution were in good agreement with those from the experimental methods and other molecular dynamics simulations but also very interesting properties of charge distributions, geometries of water molecules, hydrogen bond, diffusion coefficients, vibrational spectra are investigated by ABEEM/MM model.     

Structure and ultrafast dynamics of liquid water: a quantum mechanics/molecular mechanics molecular dynamics simulations study

A quantum mechanics/molecular mechanics molecular dynamics simulation was performed for liquid water to investigate structural and dynamical properties of this peculiar liquid. The most important region containing a central reference molecule and all nearest surrounding molecules (first coordination shell) was treated by Hartree-Fock (HF), post-Hartree-Fock [second-order Moller-Plesset perturbation theory (MP2)], and hybrid density functional B3LYP [Becke's three parameter functional (B3) with the correlation functional of Lee, Yang, and Parr (LYP)] methods. In addition, another HF-level simulation (2HF) included the full second coordination shell. Site to site interactions between oxygen-oxygen, oxygen-hydrogen, and hydrogen-hydrogen atoms of all ab initio methods were compared to experimental data. The absence of a second peak and the appearance of a shoulder instead in the gO-O graph obtained from the 2HF simulation is notable, as this feature has been observed so far only for pressurized or heated water. Dynamical data show that the 2HF procedure compensates some of the deficiency of the HF one-shell simulation, reducing the difference between correlated (MP2) and HF results. B3LYP apparently leads to too rigid structures and thus to an artificial slow down of the dynamics.     

A first principles molecular dynamics study of lithium atom solvation in binary liquid mixture of water and ammonia: structural, electronic, and dynamical properties

The preferential solvation of solutes in mixed solvent systems is an interesting phenomenon that plays important roles in solubility and kinetics. In the present study, solvation of a lithium atom in aqueous ammonia solution has been investigated from first principles molecular dynamics simulations. Solvation of alkali metal atoms, like lithium, in aqueous and ammonia media is particularly interesting because the alkali metal atoms release their valence electrons in these media so as to produce solvated electrons and metal counterions. In the present work, first principles simulations are performed employing the Car-Parrinello molecular dynamics method. Spontaneous ionization of the Li atom is found to occur in the mixed solvent system. From the radial distribution functions, it is found that the Li(+) ion is preferentially solvated by water and the coordination number is mostly four in its first solvation shell and exchange of water molecules between the first and second solvation shells is essentially negligible in the time scale of our simulations. The Li(+) ion and the unbound electron are well separated and screened by the polar solvent molecules. Also the unbound electron is primarily captured by the hydrogens of water molecules. The diffusion rates of Li(+) ion and water molecules in its first solvation shell are found to be rather slow. In the bulk phase, the diffusion of water is found to be slower than that of ammonia molecules because of strong ammonia-water hydrogen bonds that participate in solvating ammonia molecules in the mixture. The ratio of first and second rank orientational correlation functions deviate from 3, which suggests a deviation from the ideal Debye-type orientational diffusion. It is found that the hydrogen bond lifetimes of ammonia-ammonia pairs is very short. However, ammonia-water H-bonds are found to be quite strong when ammonia acts as an acceptor and these hydrogen bonds are found to live longer than even water-water hydrogen bonds.     

Structure and dynamics of the [Zn(NH3)(H2O)5]2+ complex in aqueous solution obtained by an ab initio QM/MM molecular dynamics study

A model complex of the hexahydrated zinc(ii) cation with one water substituted by ammonia in aqueous solution has been studied by hybrid ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) at the double-zeta Hartree-Fock (HF) quantum mechanical level. The first solvation shell, consisting of 5 + 1 ligand(s) at mean distances of 2.2 and 2.1 A, respectively, from the Zn(ii) ion, was found to remain stable with respect to exchange processes within the simulation time. The labile second shell consists on average of approximately 19 water molecules. For structural elucidation of the pentaaquozinc(ii) amine complex in aqueous solution several data sets such as radial distribution functions (RDF), coordination number distributions (CND) and different angular distributions (ADF, tilt and theta angle) were employed. Dynamics were characterised by the ligands' mean residence time (MRT), ion-ligand stretching frequencies and the vibrational and librational motions of water ligands. The labile second shell's MRT value decreases upon introduction of one NH(3) ligand to 7.2 ps from the 10.5 ps observed for the hexaaquozinc(ii) complex.     

Lennard-Jones parameters for the combined QM/MM method using the B3LYP/6-31G*/AMBER potential

A combined DFT quantum mechanical and AMBER molecular mechanical potential (QM/MM) is presented for use in molecular modeling and molecular simulations of large biological systems. In our approach we evaluate Lennard-Jones parameters describing the interaction between the quantum mechanical (QM) part of a system, which is described at the B3LYP/6-31+G* level of theory, and the molecular mechanical (MM) part of the system, described by the AMBER force field. The Lennard-Jones parameters for this potential are obtained by calculating hydrogen bond energies and hydrogen bond geometries for a large set of bimolecular systems, in which one hydrogen bond monomer is described quantum mechanically and the other is treated molecular mechanically. We have investigated more than 100 different bimolecular systems, finding very good agreement between hydrogen bond energies and geometries obtained from the combined QM/MM calculations and results obtained at the QM level of theory, especially with respect to geometry. Therefore, based on the Lennard-Jones parameters obtained in our study, we anticipate that the B3LYP/6-31+G*/AMBER potential will be a precise tool to explore intermolecular interactions inside a protein environment.     

QM/MM non-adiabatic decay dynamics of formamide in polar and non-polar solvents

Non-adiabatic on-the-fly dynamics simulations of the photodynamics of formamide in water and n-hexane were performed using a QM/MM approach. It was shown that steric restrictions imposed by the solvent cage do not have an influence on the initial motion which leads to the lowest energy conical intersection seam. The initial deactivation in water is faster than in n-hexane and in the gas phase. However, most of the formamide molecules in water do not reach the ground state. The reason for the deactivation inefficiency in water is traced back to a decrease of close COHOH and NHOH(2) contacts which fall in the range of hydrogen bonds. The energy deposition into H-bond breaking events leaves molecules with less energy for surmounting the CN dissociation barrier. In both solvents, after hopping to the ground state, the solvent cage keeps the HCO and NH(2) fragments or CO and NH(3) products in close proximity. Consequently, the number of trajectories where fast recombination happens is augmented with delayed recombinations that start when the dissociation fragments hit the cage wall and return back. The hot ground state formamide is formed in an internal conversion process identical to the path leading to CN photodissociation. In the case of aqueous formamide, good agreement with experimental results is achieved by combining dynamics simulations starting from the S(1) and the S(2) excited states collecting high and low energy trajectories, respectively.     

Toward accurate barriers for enzymatic reactions: QM/MM case study on p-hydroxybenzoate hydroxylase

The hydroxylation reaction catalyzed by p-hydroxybenzoate hydroxylase has been investigated by quantum mechanical/molecular mechanical (QM/MM) calculations at different levels of QM theory. The solvated enzyme was modeled (approximately 23,000 atoms in total, 49 QM atoms). The geometries of reactant and transition state were optimized for ten representative pathways using semiempirical (AM1) and density functional (B3LYP) methods as QM components. Single-point calculations at B3LYP/MM optimized geometries were performed with local correlation methods [LMP2, LCCSD(T0)] and augmented triple-zeta basis sets. A careful validation of the latter approach with regard to all computational parameters indicates convergence of the QM contribution to the computed barriers to within approximately 1 kcal mol(-1). Comparison with the available experimental data supports this assessment.     

Conformational study of the structure of free 18-crown-6

A conformational search was performed for 18-crown-6 using the CONLEX method at the MM3 level. To have a more accurate energy order of the predicted conformations, the predicted conformations were geometry optimized at the HF/STO-3G level and the 198 lowest energy conformations, according to the HF/STO-3G energy order, were geometry optimized at the HF/6-31+G level. In addition, the 47 nonredundant lowest energy conformations, according to the MP2/6-31+G energy order at the HF/6-31+G optimized geometry, hereafter the MP2/6-31+G//HF/6-31+G energy order, were geometry optimized at the B3LYP/6-31+G level. According to the MP2/6-31+G//B3LYP/6-31+G energy order, three conformations had energies lower than the experimentally known Ci conformation of 18c6. At the MP2/6-31+G//B3LYP/6-31+G level, the S6 lowest energy conformation is more stable by 1.96 kcal/mol than this Ci conformation. This was confirmed by results at the MP2/6-31+G level with an energy difference of 1.84 kcal/mol. Comparison between the structure of the S6 conformation of 18c6 and the S4 lowest energy conformation of 12-crown-4, as well as other important conformations of both molecules, is made. It is concluded that the correlation energy is necessary to have an accurate energy order of the predicted conformations. A rationalization of the conformational energy order in terms of the hydrogen bonding and conformational dihedral angles is given. It is also suggested that to have a better energy order of the predicted conformations at the MM3 level, better empirical force fields corresponding to the hydrogen bond interactions are needed.     

MM and QM/MM Modeling of Threonyl-tRNA Synthetase: Model Testing and Simulations

Aminoacyl-tRNA synthetases are centrally important enzymes in protein synthesis. We have investigated threonyl-tRNA synthetase from E. coli, complexed with reactants, using molecular mechanics and combined quantum mechanical/molecular mechanical (QM/MM) techniques. These modeling methods have the potential to provide molecular level understanding of enzyme catalytic processes. Modeling of this enzyme presents a number of challenges. The procedure of system preparation and testing is described in detail. For example, the number of metal ions at the active site, and their positions, were investigated. Molecular dynamics simulations suggest that the system is most stable when it contains only one magnesium ion, and the zinc ion is removed. Two different QM/MM methods were tested in models based on the findings of MM molecular dynamics simulations. AM1/CHARMM calculations resulted in unrealistic structures for the phosphates in this system. This is apparently due to an error of AM1. PM3/CHARMM calculations proved to be more suitable for this enzyme system. These results will provide a useful basis for future modeling investigations of the enzyme mechanism and dynamics.     

DFT:B3LYP ab initio molecular dynamics study of the Zundel and Eigen proton complexes, H5O2+ and H9O4+, in the triplet state in gas phase and solution

DFT:B3LYP ab initio molecular dynamics (MD) approach is used to elucidate the properties of the Zundel and Eigen, H5O2+ and H9O4+, proton complexes in the triplet state. The simulation considers the complexes in the gas phase (isolated complexes) and inside the clusters composed of 32, 64, and 128 water molecules, mimicking the behavior of aqueous solutions. MD simulations reveal three distinct periods. For the complex in solutions, the periods are smoothed out. The H5O2+ and H9O4+ complexes in the triplet state undergo structural rearrangements, which eventually result in hydrogen elimination. For the H5O2+, the hydrogen is eliminated from the center of the water cluster, whereas for the H9O4+ it is removed from a near-surface water molecule. The rate of hydrogen elimination decreases with increasing the number of water molecules surrounding the complex.     

Vibrational spectra and conformations of 1,4-cyclohexadiene and its oxygen analogues: ab initio and density functional calculations

The vibrational spectra and ring-puckering potential energy functions of 1,4-cyclohexadiene, 4H-pyran and 1,4-dioxin have been examined using a density functional theory (DFT) method as well as the Hartree–Fock (HF) and second-order Møller–Plesset (MP2) methods. The calculated vibrational frequencies and potential energy functions of those molecules have been compared with previously reported experimental data and MM3 results. For all three molecules, the DFT method using Becke's three-parameter functional (B3LYP) has led to the prediction of more accurate vibrational frequencies than the HF and MP2 methods. The enlargement of the basis set at the B3LYP levels has improved the accuracy of calculated vibrational frequencies. In particular, the C–O–C=C torsional force field parameters obtained from the B3LYP method have correctly predicted the ring-puckering potential energy functions of the oxygen-containing analogues, 4H-pyran and 1,4-dioxin, which could not be done by the MM3 method.     

Fragmentation-based QM/MM simulations: length dependence of chain dynamics and hydrogen bonding of polyethylene oxide and polyethylene in aqueous solutions

Molecular fragmentation quantum mechanics (QM) calculations have been combined with molecular mechanics (MM) to construct the fragmentation QM/MM method for simulations of dilute solutions of macromolecules. We adopt the electrostatics embedding QM/MM model, where the low-cost generalized energy-based fragmentation calculations are employed for the QM part. Conformation energy calculations, geometry optimizations, and Born-Oppenheimer molecular dynamics simulations of poly(ethylene oxide), PEO(n) (n = 6-20), and polyethylene, PE(n) ( n = 9-30), in aqueous solution have been performed within the framework of both fragmentation and conventional QM/MM methods. The intermolecular hydrogen bonding and chain configurations obtained from the fragmentation QM/MM simulations are consistent with the conventional QM/MM method. The length dependence of chain conformations and dynamics of PEO and PE oligomers in aqueous solutions is also investigated through the fragmentation QM/MM molecular dynamics simulations.     

Structure and dynamics of high-spin Ru in aqueous solution: Ab initio QM/MM molecular dynamics simulation

The structural and dynamical properties of high-spin Ru²⁺ in aqueous solution have been theoretically studied using molecular dynamics (MD) simulations. The conventional MD simulation based on pair potentials gives the overestimated average first shell coordination number of 9, whereas the value of 5.9 was observed when the three-body corrected function was included. A combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation has been performed to take into account the many-body effects on the hydration shell structure of Ru²⁺. The most important region, the first hydration shell, was treated by ab initio quantum mechanics at UHF level using the SBKJC VDZ ECP basis set for Ru²⁺ and the 6-31G^∗ basis sets for water. An exact coordination number of 6 for the first hydration shell was obtained from the QM/MM simulation. The QM/MM simulation predicts the average Ru²⁺–O distance of 2.42 Å for the first hydration shell, whereas the values of 2.34 and 2.46 Å are resulted from the pair potentials without and with the three-body corrected simulations, respectively. Several other structural properties representing position and orientation of the solvate molecules were evaluated for describing the hydration shell structure of the Ru²⁺ ion in dilute aqueous solution. A mean residence time of 7.1 ps was obtained for water ligands residing in the second hydration shell.