Quantum Molecular Mechanics Method Research Articles

Assessment of Embedding Schemes in a Hybrid Machine Learning/Classical Potentials (ML/MM) Approach.

Machine learning (ML) methods have reached high accuracy levels for the prediction of in vacuo molecular properties. However, the simulation of large systems solely through ML methods (such as those based on neural network potentials) is still a challenge. In this context, one of the most promising frameworks for integrating ML schemes in the simulation of complex molecular systems are the so-called ML/MM methods. These multiscale approaches combine ML methods with classical force fields (MM), in the same spirit as the successful hybrid quantum mechanics-molecular mechanics methods (QM/MM). The key issue for such ML/MM methods is an adequate description of the coupling between the region of the system described by ML and the region described at the MM level. In the context of QM/MM schemes, the main ingredient of the interaction is electrostatic, and the state of the art is the so-called electrostatic-embedding. In this study, we analyze the quality of simpler mechanical embedding-based approaches, specifically focusing on their application within a ML/MM framework utilizing atomic partial charges derived in vacuo. Taking as reference electrostatic embedding calculations performed at a QM(DFT)/MM level, we explore different atomic charges schemes, as well as a polarization correction computed using atomic polarizabilites. Our benchmark data set comprises a set of about 80k small organic structures from the ANI-1x and ANI-2x databases, solvated in water. The results suggest that the minimal basis iterative stockholder (MBIS) atomic charges yield the best agreement with the reference coupling energy. Remarkable enhancements are achieved by including a simple polarization correction.

Computational study on the metabolic activation mechanism of PeCDD by Cytochrome P450 1A1

Cytochrome P450 enzymes (CYPs) are crucial for metabolizing dioxin compounds such as 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD). Here we have applied molecular dynamic simulations (MD), quantum mechanics/molecular mechanics methods (QM/MM) and density functional theory (DFT) to investigate the metabolic activation and transformation of PeCDD catalyzed by CYP1A1. Our QM/MM calculations highlight that PeCDD can be activated by P450s through the well-known electrophilic addition mechanism with an average energy barrier of 20.9 kcal/mol. Based on the results of previous experimental studies, further conversions of ketone products and epoxidation products that are mediated by P450 enzymes were investigated through DFT calculations. Analysis of the structures via the noncovalent interactions (NCI) method and the distortion-interaction model suggests that amino acids Ser122, Ala317, Ile386 and Leu496 play important roles in the metabolic process.

Addressing the Environment Electrostatic Effect on Ballistic Electron Transport in Large Systems: A QM/MM-NEGF Approach.

The effects of the environment in nanoscopic materials can play a crucial role in device design. Particularly in biosensors, where the system is usually embedded in a solution, water and ions have to be taken into consideration in atomistic simulations of electronic transport for a realistic description of the system. In this work, we present a methodology that combines quantum mechanics/molecular mechanics methods (QM/MM) with the nonequilibrium Green's function framework to simulate the electronic transport properties of nanoscopic devices in the presence of solvents. As a case in point, we present further results for DNA translocation through a graphene nanopore. In particular, we take a closer look into general assumptions in a previous work. For this sake, we consider larger QM regions that include the first two solvation shells and investigate the effects of adding extra k-points to the NEGF calculations. The transverse conductance is then calculated in a prototype sequencing device in order to highlight the effects of the solvent.

Quantum molecular mechanics—a noniterative procedure for the fast Ab Initio calculation of closed shell systems

In this article, we advance the foundations of a strategy to develop a molecular mechanics method based not on classical mechanics and force fields but entirely on quantum mechanics and localized electron-pair orbitals, which we call quantum molecular mechanics (QMM). Accordingly, we introduce a new manner of calculating Hartree-Fock ab initio wavefunctions of closed shell systems based on variationally preoptimized nonorthogonal electron pair orbitals constructed by linear combinations of basis functions centered on the atoms. QMM is noniterative and requires only one extremely fast inversion of a single sparse matrix to arrive to the one-particle density matrix, to the electron density, and consequently, to the ab initio electrostatic potential around the molecular system, or cluster of molecules. Although QMM neglects the smaller polarization effects due to intermolecular interactions, it fully takes into consideration polarization effects due to the much stronger intramolecular geometry distortions. For the case of methane, we show that QMM was able to reproduce satisfactorily the energetics and polarization effects of all distortions of the molecule along the nine normal modes of vibration, well beyond the harmonic region. We present the first practical applications of the QMM method by examining, in detail, the cases of clusters of helium atoms, hydrogen molecules, methane molecules, as well as one molecule of HeH(+) surrounded by several methane molecules. We finally advance and discuss the potentialities of an exact formula to compute the QMM total energy, in which only two center integrals are involved, provided that the fully optimized electron-pair orbitals are known.

Calculation of the structures, stabilities, and vibrational spectra of arsenites, thioarsenites and thioarsenates in aqueous solution

Structures, stabilities and vibrational spectra have been calculated using molecular quantum mechanical methods for As(OH) 3, AsO(OH) 3, As(SH) 3, AsS(SH) 3 and their conjugate bases and for several species with partial substitution of S for O. Properties for the neutral gas-phase molecules are calculated with state-of-the-art methods which yield As L distances within 0. 01 Å and As L stretching frequencies within 10 cm −1 of experiment. Similar accuracy is obtained for neutral molecules in solution using a polarizable continuum model (PCM). For monoanions such as AsO ( OH ) 2 - and AsS ( SH ) 2 - 1 frequencies can be calculated to within 20 cm −1 of experiment using the polarizable continuum model. Multiply charged anions remain a challenge for accurate frequency calculations, but we have obtained results within the PCM model which at least semiquantitatively reproduce the available data. This allows us to assign the controversial features D, E and F in the Raman data of (Wood S. A., Tait C. D. and Janecky D. R. (2002) A Raman spectroscopic study of arsenite and thioarsenite species in aqueous solution at 25 °C. Geochem. Trans. 3, 31–39). To help in the assignment of the arsenic sulfide spectra we have also calculated energetics for the oxidation of As(III) to As(V) compounds by polysulfides, disproportionation of As(III) compounds and for the dissociation of the oxo- and thio-acids. We have determined that As(III) oxyacids can be transformed to thioacids which can in turn be oxidized to As(V) sulfides by polysulfides and that the p K a1s of the acids involved can be ordered as follows: AsS(SH) 3 < As(SH) 3 < AsO(OH) 3 < As(OH) 3 in order of increasing p K a1. We have also established from the calculated energies that the most stable form of the As(III) oxyacid in acidic aqueous solution is indeed As(OH) 3, consistent with previous assignments.

Searching for the minimum energy path in the sulfuryl transfer reaction catalyzed by human estrogen sulfotransferase: Role of enzyme dynamics

AbstractThe enzymatic transfer of a sulfuryl group from the ubiquitous biological source of sulfate 3′‐phosphoadenosine 5′‐phosphosulfate (PAPS) to estrogen is investigated by the pseudo‐bond quantum mechanical/molecular mechanical method (QM/MM) method. Calculations of the reaction path are performed starting with models based on two crystal structures, which differ in information about the cofactor and substrates. In addition, a subsequent relaxation of the enzyme was performed with the found transition state frozen, followed by redetermination of the path. An activation barrier of 22 kcal/mol is estimated. The reaction mechanism features a proton transfer from the estrogen to a catalytic histidine followed by the rate determining SO3 transfer. The mechanism found is largely dissociative. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Quantum chemical study of the mechanism of action of vitamin K epoxide reductase (VKOR)

AbstractPossible model, but simplistic, mechanisms for the action of vitamin K epoxide reductase (VKOR) are investigated with quantum mechanical methods (B3LYP/6‐311G**). The geometries of proposed model intermediates in the mechanisms are energy optimized. Finally, the energetics of the proposed (pseudo‐enzymatic) pathways are compared. We find that the several pathways are all energetically feasible. These results will be useful for designing quantum mechanical/molecular mechanical method (QM/MM) studies of the enzymatic pathway once three‐dimensional structural data are determined and available for VKOR. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Calculation of the Energetics for Oxidation of Gas-Phase Elemental Hg by Br and BrO

Recently, depletion of gas-phase elemental Hg has been observed by several research groups after polar sunrise in the atmospheric boundary layer in Arctic regions. At the same time Hg compounds have been observed to accumulate in the polar snowpack. Several different oxidation reactions involving gas-phase Br and BrO have been hypothesized to explain this process. Molecular quantum mechanical methods are here applied to evaluate the energetics of such reactions, in both the gas phase and aqueous solution. The formation of HgO from the reaction of Hg0 and BrO in the gas phase is found to be endothermic, but HgBr and HgBr2 can form exothermically through the oxidation of Hg0 by either Br atom radicals or Br2. The instability of HgO has the same cause as the low stability of HgBr compared to HgBr2, i.e., the high first IP of Hg. The calculations also indicate that HgBr2 is stable photolytically, while gas-phase HgO and HgBr are decomposed by visible light.

An averaged solvent electrostatic potential/molecular dynamics study of the influence of the electron correlation on the properties of liquid hydrogen fluoride

We study the influence that the choice of the electron correlation calculation method has on the thermodynamic, electrical, and structural properties of liquid hydrogen fluoride (HF) as obtained by Quantum Mechanics/Molecular Mechanics methods (QM/MM). We consider also the influence of the basis set and Lennard–Jones parameters. In our study we applied a non-traditional QM/MM method that makes use of the mean field approximation. We found that the influence of the correlation and basis set can be easily understood in terms of the values in the gas phase of the dipole moment and polarizabilities that they lead to. The main factor that determines the vaporization energy is the in vacuo dipole moment.

Are Neutral‐Neutral Reactions Effective for the Carbon‐Chain Growth of Cyanopolyynes and Polyacetylenes in Interstellar Space?

Ab initio molecular quantum-mechanical methods have been applied to explore the possibility of neutral-neutral reactions leading to the formation of cyanopolyynes and polyacetylenes in interstellar cloud. Potential energy surfaces for the reactions between the CN radical and polyacetylenes indicate that all reactions, C2nH2 + CN (n = 1-4), which form HC2n+1N molecules, are exothermic and have no energy barriers. We have also examined the possibility of the various product channels from the reactions C2nH2 + CN based on the thermochemical relationships. The theoretical results show that none of the product channels is exothermic except the case which produces HC2n+1N, with the carbon chain being longer than the reactant polyacetylene. Similar results are obtained for the regioselectivity of the reactions, C2nH2 + C2H (n = 1-4), to produce hydrocarbons. The only possible products from the latter reactions are shown to be HC2n+2H + H under the conditions of interstellar space. These results clearly demonstrate the importance of the neutral-neutral reactions on the carbon-chain growth of cyanopolyynes and polyacetylenes.

Aluminosilicate and borosilicate single 4-rings: Effects of counterions and water on structure, stability, and spectra

Rings containing four tetrahedrally coordinated atoms connected by bridging O atoms in a single four ring (S4R) geometry have been used to model the properties of ring species occurring in aluminosilicate and borosilicate crystals, glasses, and melts. We recently established a molecular basis for the Al avoidance, or “Loewenstein's rule,” using molecular quantum mechanical methods applied to the non-Loewenstein paired, i.e., Al … Al … Si … Si …, and the Loewenstein alternating, i.e., Al … Si … Al … Si …, geometric isomers of the Si 2Al 2O 4H 8 −2 molecular anion. We here extend this model to the Si 2Al 2O 4H 8 −2 and Si 2B 2O 4H 8 −2 molecules neutralized by various counterions such as H +, CH 3 +, Na +, and Ca 2+. Our calculations show that the paired geometry isomer can be strongly stabilized by coordination of counterions to the underbonded bridging O in the AlOAl or BOB linkages. For the Si 2Al 2 … case, coordination of H + or Ca 2+ to the underbonded O actually makes the paired geometry isomer more stable than the alternating geometry one. This result helps us to explain why the energy penalty for AlOAl bonds is smaller in Ca aluminosilicates than in Na aluminosilicates. For the Si 2B 2O 4H 8(CH 3) 2 and Si 2B 2O 4H 8Ca molecules the paired geometry is again the more stable. Underbonded O atoms in BOB linkages are found to be stabilized more strongly by counterions than are those in AlOAl linkages. This provides an explanation for the different T,T′ ordering patterns in anorthite, CaAl 2Si 2O 8, and danburite, CaB 2Si 2O 8. Our results also indicate that it may be possible to systematically synthesize gas phase and condensed phase species in which the Al avoidance rule is violated. We have also used the S4R species to model rings in Na aluminosilicate glasses and their reaction with H 2O. Calculated NMR shieldings are reduced (deshielded) by about 5–6 ppm for both Si and Al when two Na + ions are coordinated to Si 2Al 2O 12H 8 −2. Reaction of H 2O with Si 2Al 2O 12H 8Na 2 does not cause hydrolysis of the SiOAl bond or protonation of the bridging O, rather the H 2O coordinates strongly to Na + while H-bonding to the bridging O. This reaction is exoergic by about 35 kJ/mol and produces a slight shielding of the Si and a reduction in the quadrupole coupling constant of the Al. No single species was found to be consistent with all the NMR spectral data for hydrous aluminosilicate glasses.

Optical properties of solvated molecules calculated by a QMMM method Chlorophyll a and bacteriochlorophyll a

We have applied a hybrid quantum mechanical–molecular mechanical (QMMM) approach to the calculation of electronic–vibrational coupling. To test the validity of this approach, we compare results to the steady state absorption and emission spectra of chlorophyll a (Chl-a) and bacterio-chlorophyll a (BChl-a). We find that the Stokes shift and the widths of the spectra are reasonably well represented while the amplitudes of the vibrational side band in both molecules are greatly underestimated.

Open chain versus cyclic 14-electron triatomics: molecular structures and vibrational frequencies of P 2Si, P 2C, SiN 2 and Si 2S

Since the studies of Walsh in the 1950s, triatomic molecules have provided a field of investigation for the fundamentals of bonding. A general consensus has been that rings are higher in energy than open chains due to the strain associated with narrow bond angles. The 14-valence-electron triatomics P 2Si, P 2C, SiN 2, and Si 2S were investigated using ab initio molecular quantum mechanical methods. Double zeta plus polarization (DZP) and triple zeta plus double polarization (TZ2P) basis sets have been used in conjunction with self-consistent field (SCF), single and double excitation configuration interaction (CISD) and coupled cluster (CCSD) methods. The all third period P 2Si and Si 2S were found to have rings as their lowest-energy geometries. The ring geometry of P 2C is high in energy because it necessitates formation of a carbene. The ring geometry of SiN 2 is only about 5 kcal/mol above the linear SiNN isomer.

How stable is cyclobutyne? The activation energy for the unimolecular rearrangement to butatriene

The barrier height for the disappearance of the singlet ground state of cyclobutyne has been investigated using ab initio molecular quantum mechanical methods. Stationary-point geometries were determined using the two-configuration self-consistent-field (TCSCF) method in conjunction with double zeta plus polarization (DZP) basis sets. The transition state exhibits strong biradical behavior. At the DZ+P TCSCF level, the classical barrier for unimolecular rearrangement to butatriene is 55 kcal/mol. With configuration interaction including all single and double excitations with respect to both TCSCF reference configurations, the classical barrier is reduced to 51 kcal/mol. Significant further lowerings in the cyclobutyne barrier occur when coupled cluster (CC) methods are applied

Hexalithiobenzene: a D 6h equilibrium geometry with six lithium atoms in bridging positions

The synthesis of hexalithiobenzene in 53% yield from hexachlorobenzene has recently been reported by Baran and Lagow. Here, the nature of the discrete C 6Li 6 molecule has been investigated using ab initio molecular quantum-mechanical methods. A basis set approaching triplet-zeta-plus-polarization (TZP) quality was used in conjunction with the self-consistent-field (SCF) method. The lowest-energy molecular structure considered involves a benzene-like inner hexagon of carbon atoms surrounded by six Li atoms in bridging positions.

Arachno-2-Gallatetraborane(10), H2GaB3H8: an ab initio molecular quantum mechanical study

The isomers arachno-2-gallatetraborane(10) and arachno-1-gallatetraborane(10) have been studied by ab initio molecular quantum mechanical methods, following the synthesis of the 2-derivative by Downs and coworkers; substantial basis sets, e.g. Ga (14s 11p 6d/7s 5p 3d), have been used in conjunction with the self-consistent-field approximation and both structures are genuine minima, the terminal gallium structure being predicted to lie lower than its isomer by 24 kcal mol–1(1 cal = 4.184 J).

How bent can a benzene be? The molecular structure, infrared spectrum and energetics of [6]paracyclophane

Ab initio molecular quantum mechanical methods have been applied to the [6] paracyclophane molecule (C 12H 16), prepared by M. Jones and co-workers in 1974. The complete molecular structure has been predicted via the self-consistent-field (SCF) method, using both minimum and double-zeta [C(9s5p/4s2p), H(4s/2s)] basis sets. The critical geometrical parameter is the deviation φ of the benzene ring from planarity, and φ is predicted to be 17.2° and 18.6°, respectively, with the minimum and double-zeta (DZ) basis sets. The DZ angle agrees well with the experimental values, 19.4° and 20.7° , taken from crystal structures of substituted [6] paracyclophanes. These bending angles φ are 5.2° (minimum basis) and 5.1° (DZ basis) less than the analogous theoretical predictions for the less stable [5] paracyclophane. DZ SCF harmonic vibrational frequencies and infrared intensities are presented and compared with analogous predictions for benzene. The vertical excitation energies for the lowest triplet and first excited singlet states of [6] paracyclophane are also investigated. Finally the resonance energy is predicted from a suitable homodesmotic reaction and compared to the analogous result for benzene. The question of whether [6] paracyclophane is aromatic is discussed from several different perspectives.

An analysis of the infrared and Raman spectra of the formic acid dimer (HCOOH)2

Ab initio molecular quantum mechanical methods have been used to study the formic acid dimer and several isotopomers. Structures and harmonic vibrational frequencies have been predicted for the monomer, the equilibrium dimer, and the transition state for simultaneous two-hydrogen transfer. In an attempt to systematize results obtained at various levels of theory, three different basis sets were used: minimum, double-zeta (DZ), and double-zeta plus polarization (DZ+P). The predicted self-consistent-field (SCF) dissociation energies D/sub e/ are 15.1 (minimum basis), 19.3 (DZ), and 14.3 (DZ+P) kcal/mol. Further consideration of zero-point vibrational energies and finite temperature effects allows a comparison with several experimental values for ..delta..H/sub 300/. The infrared and Raman intensities (as well as the vibrational frequencies themselves) are compared with available experimental results. Where comparison is possible, the agreement is generally good. An exception occurs for v/sub 18/, the O-D stretch of the (HCOOD)/sub 2/ molecule, where it is concluded that the experimental analysis may be incorrect.

Weak intermolecular interactions: Statics and dynamics

AbstractThis contribution consists of four parts: energy calculations, physical (mainly spectroscopic) characteristics, and static and dynamic aspects of interactions leading to the formation of van der Waals species.The main, first, part includes specific comments on computational procedures for systems of different size ([number of atoms, number of electrons]: small [4, 10], medium [dozens, hundreds], large [103, 104]) and colloid systems (considering also supermolecular structures). Rigorous and simplified methods of molecular quantum mechanics can be used with the first and second groups, respectively; for larger systems, only empirical potentials and the methods of the physics of a continuum are available. The transferability of empirical potential parameters is critically examined. The role of temperature, Gibbs energy, and entropy is mentioned together with the ensemble theory. The search for stationary points on potential energy surfaces (PES) and analytical fits to PES are reviewed briefly.The second part is an outline of what is expected from computational chemistry to meet the needs of spectroscopists. The third section deals with selection rules, equilibria and the rates of processes involving van der Waals species, and the role of these species in common chemical reactivity. The crucial role of entropy is mentioned in connection with hydrophobic phenomena, entropy‐driven processes, and partitioning of substances between water and a nonpolar phase.In the final section, the role of computer experiments (molecular dynamics, Monte Carlo) is pointed out. Some shortcomings and promising features of these techniques are summarized.

Ab-initio molecular orbital study of the cis/trans conformations of the peptide bond

Ab-initio molecular orbital (MO) calculations on the model peptide, N-methylacetamide (NMA), protonated N-methylacetamide (p-NMA), and two natural dipeptides, glyclyglycine (Gly-Gly) and alanylalanine (Ala-Ala), are reported. Calculations at the STO-3G. 3-21G. and 4–31 G levels account for the predominance of the trans conformation in globular proteins. By use of p-NMA as a model precursor, the formation of the peptide bond is studied by the methods of molecular quantum mechanics. These calculations lead to the conclusion that the trans conformation should predominate, in agreement with the crystal structural data on globular proteins. In order to reduce the amount of computer time required for what are evidently the first ab-initio MO calculations on natural dipeptides, force-field calculations have been employed to obtain the conformational potential energy maps.