Molecular second-quantized Hamiltonian: Electron correlation and non-adiabatic coupling treated on an equal footing.

We introduce a new theoretical and computational framework for treating molecular quantum mechanics without the Born-Oppenheimer approximation. The molecular wavefunction is represented in a tensor-product space of electronic and vibrational basis functions, with electronic basis chosen to reproduce the mean-field electronic structure at all geometries. We show how to transform the Hamiltonian to a fully second-quantized form with creation/annihilation operators for electronic and vibrational quantum particles, paving the way for polynomial-scaling approximations to the tensor-product space formalism.

The Molpro quantum chemistry package.

Molpro is a general purpose quantum chemistry software package with a long development history. It was originally focused on accurate wavefunction calculations for small molecules but now has many additional distinctive capabilities that include, inter alia, local correlation approximations combined with explicit correlation, highly efficient implementations of single-reference correlation methods, robust and efficient multireference methods for large molecules, projection embedding, and anharmonic vibrational spectra. In addition to conventional input-file specification of calculations, Molpro calculations can now be specified and analyzed via a new graphical user interface and through a Python framework.

Novel long-chain neurotoxins from distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α-δ subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait () from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs.

Direct quantum dynamics using variational Gaussian wavepackets and Gaussian process regression.

The method of direct variational quantum nuclear dynamics in a basis of Gaussian wavepackets, combined with the potential energy surfaces fitted on-the-fly using Gaussian process regression, is described together with its implementation. Enabling exact and efficient analytic evaluation of Hamiltonian matrix elements, this approach allows for black-box quantum dynamics of multidimensional anharmonic molecular systems. Example calculations of intra-molecular proton transfer on the electronic ground state of salicylaldimine are provided, and future algorithmic improvements as well as the potential for multiple-state non-adiabatic dynamics are discussed.

Toward Accurate QM/MM Reaction Barriers with Large QM Regions Using Domain Based Pair Natural Orbital Coupled Cluster Theory.

The hydroxylation reaction catalyzed by p-hydroxybenzoate hydroxylase and the Baeyer-Villiger reaction catalyzed by cyclohexanone monooxygenase are investigated by means of quantum mechanical/molecular mechanical (QM/MM) calculations at different levels of QM theory. The geometries of the stationary points along the reaction profile are obtained from QM/MM geometry optimizations, in which the QM region is treated by density functional theory (DFT). Relative energies are determined from single-point QM/MM calculations using the domain-based local pair natural orbital coupled cluster DLPNO-CCSD(T) method as QM component.

Electron and nuclear dynamics following ionisation of modified bismethylene-adamantane.

We have simulated the coupled electron and nuclear dynamics using the Ehrenfest method upon valence ionisation of modified bismethylene-adamantane (BMA) molecules where there is an electron transfer between the two π bonds. We have shown that the nuclear motion significantly affects the electron dynamics after a few fs when the electronic states involved are close in energy. We have also demonstrated how the non-stationary electronic wave packet determines the nuclear motion, more precisely the asymmetric stretching of the two π bonds, illustrating "charge-directed reactivity".

A complete description of tunnelling using direct quantum dynamics simulation: Salicylaldimine proton transfer.

We demonstrate here conclusively that the variational multiconfiguration Gaussian (vMCG) method converges to the grid based full quantum dynamics multiconfiguration time-dependent Hartree result for a tunnelling problem in many dimensions, using the intramolecular proton transfer in salicylaldimine as a model system. The 13-dimensional model potential energy surface was obtained from Hartree Fock energies with the 6-31G* basis set and the expectation value of the flux operator along the transition mode was used as a benchmark characteristic. As well as showing excellent convergence of the vMCG method on the model surface using a local harmonic approximation and a moderate number of basis functions, we show that the direct dynamics version of the vMCG also performs very well, usually needs the same number of Gaussians to converge, and converges to exact results if those are obtained on an accurately fitted surface.

Theoretical rotation-vibration spectrum of thioformaldehyde.

We present a variational calculation of the first comprehensive T = 300 K rovibrational line list for thioformaldehyde, H2CS. It covers 41,809 rovibrational levels for states up to J(max) = 30 with vibrational band origins up to 5000 cm(-1) and provides the energies and line intensities for 547,926 transitions from the ground vibrational state to these levels. It is based on our previously reported accurate ab initio potential energy surface and a newly calculated ab initio dipole moment surface.

Quantum mechanics/molecular mechanics dual Hamiltonian free energy perturbation.

The dual Hamiltonian free energy perturbation (DH-FEP) method is designed for accurate and efficient evaluation of the free energy profile of chemical reactions in quantum mechanical/molecular mechanical (QM/MM) calculations. In contrast to existing QM/MM FEP variants, the QM region is not kept frozen during sampling, but all degrees of freedom except for the reaction coordinate are sampled. In the DH-FEP scheme, the sampling is done by semiempirical QM/MM molecular dynamics (MD), while the perturbation energy differences are evaluated from high-level QM/MM single-point calculations at regular intervals, skipping a pre-defined number of MD sampling steps.

A microiterative intrinsic reaction coordinate method for large QM/MM systems.

Intrinsic reaction coordinate (IRC) computations are a valuable tool in theoretical studies of chemical reactions, but they can usually not be applied in their current form to handle large systems commonly described by quantum mechanics/molecular mechanics (QM/MM) methods. We report on a development that tackles this problem by using a strategy analogous to microiterative transition state optimization. In this approach, the IRC equations only govern the motion of a core region that contains at least the atoms directly involved in the reaction, while the remaining degrees of freedom are relaxed after each IRC step.

Quantum mechanical/molecular mechanical study on the enantioselectivity of the enzymatic Baeyer-Villiger reaction of 4-hydroxycyclohexanone.

We report a combined quantum mechanical/molecular mechanical (QM/MM) study of the effect of mutations of the Phe434 residue in the active site of cyclohexanone monooxygenase (CHMO) on its enantioselectivity toward 4-hydroxycyclohexanone. In terms of our previously established model of the enzymatic Baeyer-Villiger reaction, enantioselectivity is governed by the preference toward the equatorial ((S)-selectivity) or axial ((R)-selectivity) conformation of the substituent at the C4 carbon atom of the cyclohexanone ring in the Criegee intermediate and the subsequent rate-limiting transition state for migration (TS2). We assess the enantiopreference by locating all relevant TS2 structures at the QM/MM level.

The cinchona primary amine-catalyzed asymmetric epoxidation and hydroperoxidation of α,β-unsaturated carbonyl compounds with hydrogen peroxide.

Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide as the oxidant, we have developed highly enantioselective Weitz-Scheffer-type epoxidation and hydroperoxidation reactions of α,β-unsaturated carbonyl compounds (up to 99.5:0.5 er).

The phenoxyl radical-water complex--a matrix isolation and computational study.

The phenoxyl radical 1 was generated in high yields by flash vacuum pyrolysis of allyl phenyl ether 2 with subsequent trapping of the products in argon at 3 K. In water-doped argon matrices, an OH···O complex between 1 and water is formed that could be characterized by IR spectroscopy. Several isotopomers of the complex were generated, and the IR spectra compared to results of density functional theory calculations.

Retaining glycosyltransferase mechanism studied by QM/MM methods: lipopolysaccharyl-α-1,4-galactosyltransferase C transfers α-galactose via an oxocarbenium ion-like transition state.

Glycosyltransferases (GTs) catalyze the highly specific biosynthesis of glycosidic bonds and, as such, are important both as drug targets and for biotechnological purposes. Despite their broad interest, fundamental questions about their reaction mechanism remain to be answered, especially for those GTs that transfer the sugar with net retention of the configuration at the anomeric carbon (retaining glycosyltransferases, ret-GTs). In the present work, we focus on the reaction catalyzed by lipopolysaccharyl-α-1,4-galactosyltransferase C (LgtC) from Neisseria meningitides.

Quantum mechanical/molecular mechanical study on the mechanism of the enzymatic Baeyer-Villiger reaction.

We report a combined quantum mechanical/molecular mechanical (QM/MM) study on the mechanism of the enzymatic Baeyer-Villiger reaction catalyzed by cyclohexanone monooxygenase (CHMO). In QM/MM geometry optimizations and reaction path calculations, density functional theory (B3LYP/TZVP) is used to describe the QM region consisting of the substrate (cyclohexanone), the isoalloxazine ring of C4a-peroxyflavin, the side chain of Arg-329, and the nicotinamide ring and the adjacent ribose of NADP(+), while the remainder of the enzyme is represented by the CHARMM force field. QM/MM molecular dynamics simulations and free energy calculations at the semiempirical OM3/CHARMM level employ the same QM/MM partitioning.