Toward Accurate Prediction of Ion Mobility in Organic Semiconductors by Atomistic Simulation.

A multiscale scheme (MLMS: Multi-Level Multi-Scale) to predict the ion mobility (µ) of amorphous organic semiconductors is proposed, which was successfully applied to the hole mobility predictions of 14 organic systems. An inverse relationship between µ and reorganization energy is observed due to local polaronic distortions. Another moderate inverse correlation between µ and distribution of site energy change exists, representing the effects of geometric flexibility. The former and the latter represent the intramolecular and intermolecular geometric effects, respectively. In addition, a linear correlation between transfer coupling and µ is observed, showing the importance of orbital overlaps between monomers. Especially, the highest hole mobility of C6-2TTN is due to its large transfer coupling. On the other hand, another high hole mobility of CBP turned out to come from the high first neighbor density (ρFND) of its first self-solvation, emphasizing the proper description of amorphous structural configurations with a sufficiently large number of monomers. In general, systems with either unusually high transfer coupling or high first neighbor density can potentially have high µ regardless of geometric effects. Especially, the newly suggested design parameter, ρFND, is pointing to a new direction as opposed to the traditional π-conjugation strategy.

Analytic Gradient for Time-Dependent Density Functional Theory Combined with the Fragment Molecular Orbital Method.

The analytic energy gradient of energy with respect to nuclear coordinates is derived for the fragment molecular orbital (FMO) method combined with time-dependent density functional theory (TDDFT). The response terms arising from the use of a polarizable embedding are derived. The obtained analytic FMO-TDDFT gradient is shown to be accurate in comparison to both numerical FMO-TDDFT and unfragmented TDDFT gradients, at the level of two- and three-body expansions. The gradients are used for geometry optimizations, molecular dynamics, vibrational calculations, and simulations of IR and Raman spectra of excited states. The developed method is used to optimize the geometry of the ground and excited electronic states of the photoactive yellow protein (PDB: 2PHY).

Accelerated Deep Learning Dynamics for Atomic Layer Deposition of Al(Me)3 and Water on OH/Si(111).

Knowledge of the detailed mechanism behind the atomic layer deposition (ALD) can greatly facilitate the optimization of the manufacturing process. Computational modeling can potentially foster the understanding; however, the presently available capabilities of the accurate ab initio computational techniques preclude their application to modeling surface processes occurring on a long time scale, such as ALD. Although the situation can be greatly improved using machine learning (ML), this technique requires an enormous amount of data for training datasets. Here, we propose an iterative protocol for optimizing ML training datasets and apply ML-assisted ab initio calculations to model surface reactions occurring during the Al(Me)3/H2O ALD process on the OH-terminated Si (111) surface. The protocol uses a recently developed low-dimensional projection technique (TDUS), greatly reducing the amount of information required to achieve high accuracy (ca. 1 kcal/mol or less) of the developed ML models. The resulting free energy landscapes reveal fine details of various aspects of the target ALD process, such as the surface proton transfer, zwitterionic surface configurations, elimination-addition/addition-elimination, and SN2 reactions as well as the role of the surface entropic and temperature effects. Simulations of adsorption dynamics predict that the maximum physisorption rate of ca. 70% is achieved at the incidence velocity urms of the reactants in the range of 15-20 Å/ps. Hence, the proposed protocol furnishes a very effective tool to study complex chemical reaction dynamics at a much reduced computational cost.

Signatures of Conical Intersection Dynamics in the Time-Resolved Photoelectron Spectrum of Furan: Theoretical Modeling with an Ensemble Density Functional Theory Method.

The non-adiabatic dynamics of furan excited in the ππ* state (S2 in the Franck-Condon geometry) was studied using non-adiabatic molecular dynamics simulations in connection with an ensemble density functional method. The time-resolved photoelectron spectra were theoretically simulated in a wide range of electron binding energies that covered the valence as well as the core electrons. The dynamics of the decay (rise) of the photoelectron signal were compared with the excited-state population dynamics. It was observed that the photoelectron signal decay parameters at certain electron binding energies displayed a good correlation with the events occurring during the excited-state dynamics. Thus, the time profile of the photoelectron intensity of the K-shell electrons of oxygen (decay constant of 34 ± 3 fs) showed a reasonable correlation with the time of passage through conical intersections with the ground state (47 ± 2 fs). The ground-state recovery constant of the photoelectron signal (121 ± 30 fs) was in good agreement with the theoretically obtained excited-state lifetime (93 ± 9 fs), as well as with the experimentally estimated recovery time constant (ca. 110 fs). Hence, it is proposed to complement the traditional TRPES observations with the trXPS (or trNEXAFS) measurements to obtain more reliable estimates of the most mechanistically important events during the excited-state dynamics.

Computation of Molecular Electron Affinities Using an Ensemble Density Functional Theory Method.

The computation of electron attachment energies (electron affinities) was implemented in connection with an ensemble density functional theory method, the state-interaction state-averaged spin-restricted ensemble-referenced Kohn-Sham (SI-SA-REKS or SSR) method. With the use of the extended Koopmans' theorem, the electron affinities and the respective Dyson orbitals are obtained directly for the neutral molecule, thus avoiding the necessity to compute the ionized system. Together with the EKT-SSR (extended Koopmans' theorem-SSR) method for ionization potentials, which was developed earlier, EKT-SSR for electron affinities completes the implementation of the EKT-SSR formalism, which can now be used for obtaining electron detachment as well as the electron attachment energies of molecules in the ground and excited electronic states. The extended EKT-SSR method was tested in the calculation of several closed-shell molecules. For the molecules in the ground states, the EKT-SSR energies of Dyson's orbitals are virtually identical to the energies of the unoccupied orbitals in the usual single-reference spin-restricted Kohn-Sham calculations. For the molecules in the excited states, EKT-SSR predicts an increase of the most positive electron affinity by approximately the amount of the vertical excitation energy. The electron affinities of a number of diradicals were calculated with EKT-SSR and compared with the available experimental data. With the use of a standard density functional (BH&HLYP), the EKT-SSR electron affinities deviate on average by ca. 0.2 eV from the experimental data. It is expected that the agreement with the experiment can be improved by designing density functionals parametrized for ionization energies.

Structural or population dynamics: what is revealed by the time-resolved photoelectron spectroscopy of 1,3-cyclohexadiene? A study with an ensemble density functional theory method.

Time-resolved photoelectron spectra during the photochemical ring-opening reaction of 1,3-cyclohexadiene (CHD) are modeled by an ensemble density functional theory (eDFT) method. The computational methodology employed in this work is capable of correctly describing the multi-reference effects arising in the ground and excited electronic states of molecules, which is important for the correct description of the ring-opening reaction of CHD. The geometries of molecular species along the non-adiabatic molecular dynamics (NAMD) trajectories reported in a previous study of the CHD photochemical ring-opening were used in this work to calculate the ionization energies and the respective Dyson orbitals for all possible ionization channels. The obtained theoretical time-resolved spectra display decay characteristics in a reasonable agreement with the experimental observations; i.e., the decay (and rise) of the most mechanistically significant signals occurs on the timescale of 100-150 fs. This is very different from the excited state population decay characteristics (τS1 = 234 ± 8 fs) obtained in the previous NAMD study. The difference between the population decay and the decay of the photoelectron signal intensity is traced back to the geometric transformation that the molecule undergoes during the photoreaction. This demonstrates the importance of including the geometric information in interpretation of the experimental observations.

Recent developments in the general atomic and molecular electronic structure system.

A discussion of many of the recently implemented features of GAMESS (General Atomic and Molecular Electronic Structure System) and LibCChem (the C++ CPU/GPU library associated with GAMESS) is presented. These features include fragmentation methods such as the fragment molecular orbital, effective fragment potential and effective fragment molecular orbital methods, hybrid MPI/OpenMP approaches to Hartree-Fock, and resolution of the identity second order perturbation theory. Many new coupled cluster theory methods have been implemented in GAMESS, as have multiple levels of density functional/tight binding theory. The role of accelerators, especially graphical processing units, is discussed in the context of the new features of LibCChem, as it is the associated problem of power consumption as the power of computers increases dramatically. The process by which a complex program suite such as GAMESS is maintained and developed is considered. Future developments are briefly summarized.

Low-dimensional projection approach for efficient sampling of molecular recognition and polymer aggregation.

The one-dimensional projection (ODP) approach is extended to two-dimensional umbrella sampling (TDUS) and is applied to three different complex systems in combination with a reactive force field (ReaxFF). TDUS is capable of showing detailed features of the free-energy surface (FES) of the double-proton transfer of the acetic acid dimer. It also revealed the direct relationship between the types of hydrogen bonding and binding strengths in the case of adrenaline molecular recognition by SIVSF (Serine, Isoleucine, Valine, Cysteine, and Phenylalanine). The study of polymer aggregation using TDUS shows that aggregation is preferred with a less-polar solvent, which is also consistent with the experimental observation of a tape-casting process. Therefore, TDUS can be generally useful in FES explorations from simple chemical reactions to complex processes of molecular recognition and polymer aggregation.

Geometry Optimization, Transition State Search, and Reaction Path Mapping Accomplished with the Fragment Molecular Orbital Method.

Recent development of the fragment molecular orbital (FMO) method related to energy gradients, geometry optimization, transition state search, and chemical reaction mapping is summarized. The frozen domain formulation of FMO is introduced in detail, and the structure of related GAMESS input files for FMO is described.

FMOxFMO: Elucidating Excitonic Interactions in the Fenna-Matthews-Olson Complex with the Fragment Molecular Orbital Method.

In order to study Förster resonance energy transfer (FRET), the fragment molecular orbital (FMO) method is extended to compute electronic couplings between local excitations via the excited state transition density model, enabling efficient calculations of nonlocal excitations in a large molecular system and overcoming the previous limitation of being able to compute only local excitations. The results of these simple but accurate models are validated against full quantum calculations without fragmentation. The developed method is applied to a very important photosynthetic pigment-protein complex, the Fenna-Matthews-Olson complex (FMOc), that is responsible for the energy transfer from a chlorosome to the reaction center in the green sulfur bacteria. Absorption and circular dichroism spectra of FMOc are simulated, and the role of the molecular environment on the excitations is revealed.

Simulations of infrared and Raman spectra in solution using the fragment molecular orbital method.

Analytic second derivatives of the energy with respect to nuclear coordinates are derived for the fragment molecular orbital method combined with the polarizable continuum model. Harmonic frequencies, infrared intensities and normal Raman activities of large molecular systems in solution can be evaluated. Periodic trends on SN2 chemical reactions are elucidated. The accuracy of the developed method is established in comparison to full calculations without fragmentation. The method is applied to ionic liquids and crambin (PDB: ). Solvent effects on the vibrational frequencies are discussed.

Efficient implementations of analytic energy gradient for mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT).

Analytic energy gradients of individual singlet and triplet states with respect to nuclear coordinates are derived and implemented for the collinear mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT), which eliminates the problematic spin-contamination of SF-TDDFT. Dimensional-transformation matrices for the singlet and triplet response spaces are introduced, simplifying the subsequent derivations. These matrices enable the general forms of MRSF-TDDFT equations to be similar to those of SF-TDDFT, suggesting that the computational overhead of singlet or triplet states for MRSF-TDDFT is nearly identical to that of SF-TDDFT. In test calculations, the new MRSF-TDDFT yields quite different optimized structures and energies as compared to SF-TDDFT. These differences turned out to mainly come from the spin-contamination of SF-TDDFT, which are largely cured by MRSF-TDDFT. In addition, it was demonstrated that the clear separation of singlet states from triplets dramatically simplifies the location of minimum energy conical intersection. As a result, it is clear that the MRSF-TDDFT has advantages over SF-TDDFT in terms of both accuracy and practicality. Therefore, it can be a preferred method, which is readily applied to other "black-box" type applications, such as the minimum-energy optimization, reaction path following, and molecular dynamics simulations.

Development of a new parameter optimization scheme for a reactive force field based on a machine learning approach.

Reactive molecular dynamics (MD) simulation is performed using a reactive force field (ReaxFF). To this end, we developed a new method to optimize the ReaxFF parameters based on a machine learning approach. This approach combines the k-nearest neighbor and random forest regressor algorithm to efficiently locate several possible ReaxFF parameter sets. As a pilot test of the developed approach, the optimized ReaxFF parameter set was applied to perform chemical vapor deposition (CVD) of an α-Al2 O3 crystal. The crystal structure of α-Al2 O3 was reasonably reproduced even at a relatively high temperature (2000 K). The reactive MD simulation suggests that the (11 2 ¯ 0) surface grows faster than the (0001) surface, indicating that the developed parameter optimization technique could be used for understanding the chemical reaction in the CVD process. © 2019 Wiley Periodicals, Inc.

Nodular gastritis in association with gastric cancer development before and after Helicobacter pylori eradication.

BACKGROUND AND AIM: Nodular gastritis is caused by Helicobacter pylori infection and is associated with the development of diffuse-type gastric cancer. This study examined the clinical characteristics of patients with nodular gastritis, including cancer incidence before and after H. pylori eradication. METHODS: This was a retrospective study of patients who underwent upper endoscopy and were positive for H. pylori infection. We examined the clinical findings and follow-up data after H. pylori eradication in patients with and without nodular gastritis. RESULTS: Of the 674 patients with H. pylori infections, nodular gastritis was observed in 114 (17%). It was more prevalent in women (69%) and young adults. Among patients with nodular gastritis, six (5%) had gastric cancer, all of which were of the diffuse type. Among the 19 (4%) patients with gastric cancer and no nodular gastritis, 16 had intestinal-type cancer. White spot aggregates in the corpus, a specific finding in patients with nodular gastritis, were more frequently observed in patients with gastric cancer than in those without (83% vs 26%, P = 0.0025). Of 82 patients with nodular gastritis who had H. pylori eradicated successfully, none developed gastric cancer over a 3-year follow-up period, while 7 (3%) of 220 patients without nodular gastritis developed gastric cancer after H. pylori eradication. CONCLUSIONS: In patients with nodular gastritis, white spot aggregates in the corpus may indicate a higher risk of developing diffuse-type gastric cancer. Nodular gastritis may be an indication for eradication therapy to reduce the risk of cancer development after H. pylori eradication.

Analytic second derivatives for the efficient electrostatic embedding in the fragment molecular orbital method.

The analytic second derivatives of the energy with respect to nuclear coordinates are developed for restricted Hartree-Fock and density functional theory, based on the two-body fragment molecular orbital method (FMO) and combined with the electrostatic embedding potential, self-consistently determined by point charges for far separated fragments and electron densities for near fragments. The accuracy of the method is established with respect to FMO using the exact embedding potential based on electron densities and to full calculations without fragmentation. The computational efficiency of parallelization is measured on the K supercomputer and the method is applied to simulate infrared spectra of two proteins, Trp-cage (PDB: 1L2Y) and crambin (1CRN). The nature of the vibrations in the Amide I peak of crambin and the Tyr symmetric stretch peak in Trp-cage are analyzed in terms of localized vibrations. © 2018 Wiley Periodicals, Inc.

Efficient Geometry Optimization of Large Molecular Systems in Solution Using the Fragment Molecular Orbital Method.

The analytic gradient is derived for the frozen domain formulation of the fragment molecular orbital (FMO) method combined with the polarizable continuum model. The accuracy is tested in comparison to full FMO calculations for a representative set of systems in terms of the gradient accuracy, protein-ligand binding energies, and optimized structures. The frozen domain method reproduced geometries optimized with full FMO within 0.03-0.09 Å in terms of reduced mean square deviations, whereas a single-point gradient calculation is accelerated by the factor of 38 (Trp-cage protein in explicit solvent, PDB: 1L2Y ) and 12 (crambin, PDB: 1CRN ). The method is applied to a geometry optimization of the K-Ras protein-ligand complex (4Q03) using two domain definitions, and the optimized structures are consistent with experiment. Pair interaction analysis is used to identify residues important in binding the ligand.

Analytic second derivative of the energy for density-functional tight-binding combined with the fragment molecular orbital method.

The analytic second derivative of the energy is developed for the fragment molecular orbital (FMO) method combined with density-functional tight-binding (DFTB), enabling simulations of infrared and Raman spectra of large molecular systems. The accuracy of the method is established in comparison to full DFTB without fragmentation for a set of representative systems. The performance of the FMO-DFTB Hessian is discussed for molecular systems containing up to 10 041 atoms. The method is applied to the study of the binding of α-cyclodextrin to polyethylene glycol, and the calculated IR spectrum of an epoxy amine oligomer reproduces experiment reasonably well.

Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water Demonstrated with the Fragment Molecular Orbital Method.

The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted second-order Møller-Plesset perturbation theory, as well as for both restricted and unrestricted Hartree-Fock and density functional theory. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262,144 CPU cores are also discussed.

Large-Scale Quantum-Mechanical Molecular Dynamics Simulations Using Density-Functional Tight-Binding Combined with the Fragment Molecular Orbital Method.

The fully analytic gradient is developed for density-functional tight-binding (DFTB) combined with the fragment molecular orbital (FMO) method (FMO-DFTB). The response terms arising from the coupling of the electronic state to the embedding potential are derived, and the gradient accuracy is demonstrated on water clusters and a polypeptide. The radial distribution functions (RDFs) obtained with FMO-DFTB are found to be similar to those from conventional DFTB, while the computational cost is greatly reduced; for 256 water molecules one molecular dynamics (MD) step takes 73.26 and 0.68 s with full DFTB and FMO-DFTB, respectively, showing a speed-up factor of 108. FMO-DFTB/MD is applied to 100 ps MD simulations of liquid hydrogen halides and is found to reproduce experimental RDFs reasonably well.

Simulations of Chemical Reactions with the Frozen Domain Formulation of the Fragment Molecular Orbital Method.

The fully analytic first and second derivatives of the energy in the frozen domain formulation of the fragment molecular orbital (FMO) were developed and applied to locate transition states and determine vibrational contributions to free energies. The development is focused on the frozen domain with dimers (FDD) model. The intrinsic reaction coordinate method was interfaced with FMO. Simulations of IR and Raman spectra were enabled using FMO/FDD by developing the calculation of intensities. The accuracy is evaluated for S(N)2 reactions in explicit solvent, and for the free binding energies of a protein-ligand complex of the Trp cage protein (PDB: 1L2Y ). FMO/FDD is applied to study the keto-enol tautomeric reaction of phosphoglycolohydroxamic acid and the triosephosphate isomerase (PDB: 7TIM ), and the role of amino acid residue fragments in the reaction is discussed.