Electronic structure and bonding properties of the Group 12 dications M2 2+ (M = Zn, Cd, Hg) are investigated and electron density-derived quantities are used to characterize the metastability of these species. Of particular interest are the complementary descriptions afforded by the Laplacian of the electron density ∇2 ρ(r) and the one-electron Bohm quantum potential (Q =  [Formula: see text] ) along the bond path. Further, properties derived from the pair density including the localization-delocalization matrices (LDMs) and the interacting quantum atoms (IQA) energies are analyzed within the framework of the quantum theory of atoms in molecules (QTAIM). From the crossing points of the singlet (ground) and triplet (excited) potential energy curves, the barriers for dissociation (BFD) are estimated to be 25.2 kcal/mol (1.09 eV) for Zn2 2+ , 22.8 kcal/mol (0.99 eV) for Cd2 2+ , and 26.4 kcal/mol (1.14 eV) for Hg2 2+ . For comparison and benchmarking purposes, the case of N2 2+ is considered as a texbook example of metastability. At the equilibrium geometries, LDMs, which are used here as an electronic fingerprinting tool, discriminate and group together Group 12 M2 2+ from its isoelectronic Group 11 M2 . While "classical" bonding indices are inconclusive in establishing regions of metastability in the bonding, it is shown that the one-electron Bohm quantum potential is promising in this regard.

Antipsychotics represent an effective therapy for schizophrenia (a chronic mental disorder). Their benefits are related to the interaction of the drugs with dopamine D2 receptor (D2R). Antipsychotics are classified as agonists or antagonists. One of the working hypotheses is that there is a charge transfer process between the drugs and the receptors, which is different for agonists and antagonists. To have more insight into the nature of the interaction of these molecules and the differences between agonists and antagonists, we analyze the interaction of graphene with three molecules: dopamine, pramipexole (an agonist of dopamine), and risperidone (an antagonist of dopamine). The idea is to use graphene as a simple model to analyze the charge transfer process of these three drugs. Optimized structures, atomic charges, and Density of States results indicate that global charges of dopamine and pramipexole are similar, while for risperidone, it is more than double. Pramipexole is an agonist, and the charge transfer process is similar to that of dopamine. Risperidone is an antagonist, and the charge transfer process is different from dopamine. The charge transfer is more significant with risperidone than with dopamine, and this could be related to the mechanism of action. This is in agreement with the working hypotheses that establish that it is possible to distinguish between agonists and antagonists since they have different capacity to transfer charge.

In hybrid particle-field (hPF) simulations (J. Chem. Phys., 2009 130, 214106), the entangled dynamics of polymer melts is lost due to chain crossability. Chains cross, because the field-treatment of the nonbonded interactions makes them effectively soft-core. We introduce a multi-chain slip-spring model (J. Chem. Phys., 2013 138, 104907) into the hPF scheme to mimic the topological constraints of entanglements. The structure of the polymer chains is consistent with that of regular molecular dynamics simulations and is not affected by the introduction of slip-springs. Although slight deviations are seen at short times, dynamical properties such as mean-square displacements and reorientational relaxation times are in good agreement with traditional molecular dynamics simulations and theoretical predictions at long times.

Calcineurin (CaN) is a eukaryotic serine/threonine protein phosphatase activated by both Ca2+ and calmodulin (CaM), including intrinsically disordered region (IDR). The region undergoes folding into an α-helix form in the presence Ca2+ -loaded CaM. To sample the ordered structure of the IDR by conventional all atom model (AAM) molecular dynamics (MD) simulation, the IDR and Ca2+ -loaded CaM must be simultaneously treated. However, it is time-consuming task because the coupled folding and binding should include repeated binding and dissociation. Then, in this study, we propose novel multi-scale divide-and-conquer MD (MSDC-MD), which combines AAM-MD and coarse-grained model MD (CGM-MD). To speed up the conformation sampling, MSDC-MD simulation first treats the IDR by CGM to sample conformations from wide conformation space; then, multiple AAM-MD in a limited area is initiated using the resultant CGM conformation, which is reconstructed by homology modeling method. To investigate performance, we sampled the ordered conformation of the IDR using MSDC-MD; the root-mean-square distance (RMSD) with respect to the experimental structure was 2.23 Å.

A mathematical aspect of the anharmonic downward distortion following (ADDF) path is discussed. The ADDF method is utilized as an automated reaction path search method, which can explore transition state geometries on a potential energy surface from a potential minimum. We show that the maximum number of the ADD stationary paths intersecting the potential minimum is 2f + 1  - 2, where f denotes the degree of freedom of the system. We also show that the bifurcation of the ADD stationary path is essential to detect all the transition states connected from a given minimum. The ADDF computation is demonstrated for a H2 O molecule in which pitchfork bifurcation is observed.

Predicting protein function and structure from sequence remains an unsolved problem in bioinformatics. The best performing methods rely heavily on evolutionary information from multiple sequence alignments, which means their accuracy deteriorates for sequences with a few homologs, and given the increasing sequence database sizes requires long computation times. Here, a single-sequence-based prediction method is presented, called ProteinUnet, leveraging an U-Net convolutional network architecture. It is compared to SPIDER3-Single model, based on long short-term memory-bidirectional recurrent neural networks architecture. Both methods achieve similar results for prediction of secondary structures (both three- and eight-state), half-sphere exposure, and contact number, but ProteinUnet has two times fewer parameters, 17 times shorter inference time, and can be trained 11 times faster. Moreover, ProteinUnet tends to be better for short sequences and residues with a low number of local contacts. Additionally, the method of loss weighting is presented as an effective way of increasing accuracy for rare secondary structures.

Optically active small organic molecules are computationally designed using the ChemTS python library developed by Tsuda and collaborators, which utilizes a combined Monte Carlo tree search (MCTS) and recurrent neural network model. Geometry optimization and excited-state calculations are performed for each generated molecule, following which the excitation energy and dissymmetry factors are computed to evaluate the score function in the MCTS process. Using this procedure, molecules not contained in existing databases are generated. Molecules having either high dissymmetry factors or high transition dipole strengths can be generated depending on the choice of the score function. In a single trajectory with 100,000 trials, mutually similar high-scoring molecules are generated frequently after the initial 15,000-20,000 trials. This indicates that it is better to sample high-scoring molecules from several trajectories having a modest number of trials each than from a single trajectory having a large number of trials.

A simple practical method to compute both d-d and metal-to-ligand charge-transfer (MLCT) excited states of iron(II) polypyridyl complexes is proposed for use in simulation studies. Specifically, a model electronic Hamiltonian developed previously for d-d excited states of [Fe(bpy)3 ]2+ is extended to deal with low-lying MLCT excited states simultaneously by including the MLCT electronic configurations into the basis functions of the model Hamiltonian. As a first attempt, parameters in the model Hamiltonian matrix elements are determined by using density functional theory (DFT) and time-dependent (TD-)DFT calculation results as benchmarks. To examine the performance of the model Hamiltonian, the potential energy curves along the interpolation between the lowest singlet and quintet state structures are compared to those from the (TD-)DFT calculations and to those from CASPT2 calculations in literature. The electronic absorption spectrum computed through molecular dynamics simulation is compared to the experimental spectrum. The spin-orbit couplings at the ground state structure are also compared to those from wavefunction-based ab initio electronic structure calculations. The results indicate that the constructed model Hamiltonian provides reasonable information on both the low-lying d-d and MLCT excited states of [Fe(bpy)3 ]2+ .

This article presents a thorough density functional theory based comparative study on nitrogen-rich 5-aminotetrazole alkali metal salts M 5-At (M = Li, K, Rb, Cs). The calculated structural parameters using plane-wave pseudopotential method are consistent with the experimental results. The computed vibrational frequencies at ambient pressure show that vibrational modes in high energy region are due the NH bond of NH2 group. Pressure variation IR spectra of these materials show clear frequency shifts where Li 5-At shows an overall red shift below 900 cm-1 contrary to the blue shift seen in other materials in this range. The born effective charge values reveal the presence of strong covalency between N, H, and C atoms whereas an increased ionic nature is seen as the atomic number of metal atoms increases. Furthermore, we used full potential linear augmented plane wave (FP-LAPW) method for calculating electronic structure and optical properties with TB-mBJ potential which provides an enhanced band gap for all materials compared to standard GGA functional. Electronic structure calculation reveals that all the compounds are indirect band gap insulators with the exception of Li 5-At. The computed partial density of states show mixed ionic-covalent nature in metal-N/C bonds and covalent nature in NC bonds. In addition, we are also presenting the optical properties such as real and imaginary dielectric constant, absorption, refraction, reflection, loss spectrum as functions of photon energy. From the optical properties we can conclude that all the studied compounds are optically anisotropic in nature and are good absorbers in the ultraviolet (UV) region.

We propose a canonical sampling method to refine metadynamics simulations a posteriori, where the hills obtained from metadynamics are used as a time-invariant bias potential. In this way, the statistical error in the computed reaction barriers is reduced by an efficient sampling of the collective variable space at the free energy level of interest. This simple approach could be useful particularly when two or more free energy barriers are to be compared among chemical reactions in different or competing conditions. The method was then applied to study the acid dependence of polyalcohol dehydration reactions in high-temperature aqueous solutions. It was found that the reaction proceeds consistently via an SN 2 mechanism, whereby the free energy of protonation of the hydroxyl group created as an intermediate is affected significantly by the acidic species. Although demonstration is shown for a specific problem, the computational method suggested herein could be generally used for simulations of complex reactions in the condensed phase.

High performance global exploration of isomers and isomerization channels on the quantum chemical potential energy surface (PES) is performed for H5 C2 NO2 by using the scaled hypersphere search-anharmonic downward distortion following (SHS-ADDF) method. A multi-node operation, NeoGRRM, has achieved high performance exploration calculations for the large system by submitting SHS-ADDF sub-jobs into many cores in parallel and unifying the results of sub-jobs into the total lists of the main-job. Global exploration of equilibrium (EQ) and transition-state structures at the level of B3LYP/6-31G(d) gave 3210 EQs and 23278 TSs. Nine compounds were found in the low energy regions of 0-100 kJ/mol; the lowest energy compound is N-methylcarbamic acid, the second is methyl carbamate, and the third is glycine (the most fundamental amino acid). Interconversion pathways between the conformers of each of the low energy compounds were surveyed. Isomerization channels around glycine were explored in detail. The lowest energy barriers around some of the EQs turned to be negative after zero-point energy corrections. This indicates that those structures cannot exist as independent structures because they spontaneously collapse into more stable structures. The global PES search showed various interesting dissociating channels which indicate synthon reaction pathways in the reverse directions.

It was previously reported that Laplace transformed local CC2 (LCC2*) provided the best agreement (MAE = 0.145 eV) when comparing vertical excitation energies to experimental λmax for a benchmark set of 17 BODIPY/Aza-BODIPY molecules. However, these energies did not agree with values obtained from canonical CC2. Here we report LCC2* computations of vertical excitation energies on the same benchmark set of molecules using a newly implemented treatment of the ground state. Comparison with resolution-of-identity approximate coupled cluster to second-order (RI-CC2) results demonstrate that the new LCC2* results agree quantitatively. Furthermore, these values can easily be corrected empirically to also provide excellent agreement with the experiment. We show that the local algebraic diagrammatic construction to second-order (LADC(2)) method exhibits the same differences between implementations as seen for LCC2. The source of the difference is traced to an improved treatment of the ground state in the local methods, which decreases agreement with the experiment (as attributed to a fortuitous cancellation of errors) but significantly improves agreement with RI-CC2. While the absolute vertical excitation energies now show larger deviations, there remains a strong linear correlation between the LCC2* results and the experiment. For the 17 BODIPY/Aza-BODIPY molecules vertical excitation energies are determined using DLPNO-STEOM-CCSD and shown to have excellent agreement with experimental λmax (MAE = 0.145 eV), which is the best of all the single-reference methods. The vertical excitation energies are determined using LCC2*, empirically corrected LCC2*, and RI-CC2 for a series of eight large BODIPYs and Aza-BODIPYs.

FFLUX is a biomolecular force field under construction, based on Quantum Chemical Topology (QCT) and machine learning (kriging), with a minimalistic and physically motivated design. A detailed analysis of the forces within the kriging models as treated in FFLUX is presented, taking as a test example a liquid water model. The energies of topological atoms are modeled as 3Natoms -6 dimensional potential energy surfaces, using atomic local frames to represent the internal degrees of freedom. As a result, the forces within the kriging models in FFLUX are inherently N-body in nature where N refers to Natoms . This provides a fuller picture that is closer to a true quantum mechanical representation of interactions between atoms. The presented computational example quantitatively showcases the non-negligible (as much as 9%) three-body nature of bonded forces and angular forces in a water molecule. We discuss the practical impact on the pressure calculation with N-body forces and periodic boundary conditions (PBC) in molecular dynamics, as opposed to classical force fields with two-body forces. The equivalence between the PBC-related correction terms in the general virial equation is shown mathematically.

The umbrella sampling (US) approach has been demonstrated to be a very efficient method for estimating the ligand-binding affinity. However, most of the calculated values overestimate experimental ones that are probably caused by the inaccurate representation of the interaction between the ligand and the surrounding molecules. The issue can be resolved via the implementation aspects of λ-alteration simulation into the US approach, which we call the λ-dependent umbrella sampling (λUS) scheme. In particular, the electrostatic and van der Waals interactions were simultaneously changed by using the coupling parameter λ during λUS simulations. The mean value of obtained results, ∆GUSλ=0.20 =  - 11.59 ± 1.51 kcal mol-1 , is in good fitting to the mean value of respective experiments, ∆GEXP =  - 11.26 ± 0.89 kcal mol-1 . Moreover, the correlation between the proposed approach and experiment is quite good with a value of RUSλ=0.20 = 0.82 ± 0.10 . The λUS scheme significantly enhances the calculated accuracy since the RMSE of the proposed scheme is smaller than traditional US simulations, RMSEUSλ=0.20 = 2.99 ± 0.82 kcal mol-1 versus RMSEUSλ=0.00 = 5.48 ± 0.81 kcal mol-1 . Furthermore, the precision is increased since the computed error via λUS approach, δUSλ=0.20 = 1.51 kcal mol-1 , was smaller than those of the US simulation, δUSλ=0.00 = 1.78 kcal mol-1 . Overall, the proposed approach perhaps provides an efficient way to accurately and precisely estimate the ligand-binding free energy.

The present study concerns the technical aspects of obtaining the energetics for the E4 state of nitrogenase, the enzyme that fixes N2 in nature. EPR experiments have shown that the critical E4 structure that activates N2 should contain two bridging hydrides in the FeMo-cofactor. It is furthermore in equilibrium with a structure where the two hydrides have been released and N2 binds. These observations led to the suggestion that E4 should have two bridging hydrides and two protonated sulfides. It is important to note that the structure for E4 has not been determined, but only suggested. For a long time, no DFT study led to the suggested structure, independent of which functional was used. However, in two recent DFT studies a good agreement with the experimental suggestion was claimed to have been obtained. In one of them the TPSS functional was used. That was the first out of 11 functionals tried that led to the experimentally suggested structure. In the second of the recent DFT studies, a similar conclusion was reached using the TPSSh functional. The conclusions in the recent studies have here been studied in detail, by calculating a critical energetic value strongly implied by the same EPR experiments. Both the TPSS and TPSSh functionals have been used. The present calculations suggest that those DFT functionals would not lead to agreement with the experimental EPR results either.

Two new structural motifs of the B24 clusters are constructed by use of the leapfrog transformation. The resulting leapfrog B24 has either a bowl shape with a square vacancy or a quasi-planar 2D close-packed triangular boron sheet. The neutral and ionic forms of the latter are found to be more stable than their homologous leapfrog bowl clusters, with the exception of the dicationic B24 +2 . While the leapfrog isomer is less stable than the tubular double ring in the neutral state, it becomes competitive in some ionic states. The nucleus independent chemical shift, electron localization function, ring current maps and the electronic structure of leapfrog B24 clusters reveal them to behave as aromatics.

Despite the belief that noble gases (Ng) are completely inert and cannot form stable molecules, a variety of Ng compounds have been reported under laboratory conditions and others were recently detected in the interstellar media, raising interest in knowing and studying their bond nature and the physicochemical properties associated with their stability. In the present work, a systematic analysis of the thermodynamic stability of noble gas halide cations (NgX+ ) at the CCSD(T)/def2-QZVP level have been performed. In addition, chemical bond was characterized through Natural Bonding Theory (NBO), Quantum Theory of Atoms in Molecules (QTAIM) and Energy Decomposition Analysis (EDA) with relativistic corrections. All methods suggest that NgX+ compounds possess a strong covalent bond. However, results show that only compounds containing Ar-Rn atoms are thermodynamic stable with a highly energetic and endergonic dissociation process. For these reasons, it is possible to suggest that several compounds that have not yet been reported could be obtained at the laboratory level or observed in the interstellar medium.

Molecular dynamics on the complexes of inhibitors with Zn-metalloproteins are a privileged area of applications of polarizable molecular mechanics potentials. With which accuracy could these reproduce the QC intermolecular interaction energies in the two mono-zinc cores and in the dizinc core, toward full-fledged MD simulations on the entire protein complexes? We considered the complexes of the extended recognition site of a Zn-dependent metallo-β-lactamase, VIM-2, produced by bacteria responsible for nosocomial infections, with five newly synthesized inhibitors sharing an original dizinc binding group, 1,2,4-triazole-3-thione (TZT). We considered the energy-minimized structures of each of the five VIM-2 complexes obtained with the SIBFA potential. Energy decomposition analyses (EDA) at the HF level enabled to compare the QC and the SIBFA ΔE values and their contributions in the zinc cores, with and without TZT, totaling 30 complexes. With one exception, the ΔE(QC) values were reproduced with relative errors <1.5%. We next considered the complex of the entire inhibitors with an extended model of VIM-2 recognition site, totaling up to 280 atoms. ΔE(SIBFA) could closely reproduce ΔE(QC). EDA analyses were resumed on the complexes of each inhibitor arm with its interacting VIM-2 residues. As a last step, EDA results at correlated levels were analyzed for the mono- and dizinc sites enabling comparisons with dispersion-augmented ΔE(SIBFA) and correlated multipoles and polarizabilities. Closely reproducing ΔE(QC) and the contrasting trends of its individual contributions should enable for dependable free energy perturbation studies and comparisons to recent experimental ΔG values, limiting as much as possible the reliance on error compensations.