The Thole induced point dipole model is combined with three different point charge fitting methods, Merz–Kollman (MK), charges from electrostatic potentials using a grid (CHELPG), and restrained electrostatic potential (RESP), and two multipole algorithms, distributed multipole analysis (DMA) and Gaussian multipole model (GMM), which can be used to describe the electrostatic potential (ESP) around molecules in molecular mechanics force fields. This is done to study how the different methods perform when intramolecular polarizability contributions are self-consistently removed from the fitting done in the force field parametrization. It is demonstrated that the polarizable versions of the partial charge models provide a good compromise between accuracy and computational efficiency in describing the ESP of small organic molecules undergoing conformational changes. For the point charge models, the inclusion of polarizability reduced the the average root mean square error of ESP over the test set by 4–10%. © 2015 Wiley Periodicals, Inc.

We combine the Thole induced point dipole model with three different point charge fitting methods and two multipole algorithms. This is done to investigate how the different methods perform when used as a basis for a polarizable force field. We compare the methods based on how well they are able to reproduce the electrostatic potential of a molecule (1) around the minimum energy conformation of a molecule and (2) when the molecule undergoes conformational changes.

We present the molecular dynamics study of benzene molecules confined into the single wall carbon nanotube. The local structure and orientational ordering of benzene molecules are investigated. It is found that the molecules mostly group in the middle distance from the axis of the tube to the wall. The molecules located in the vicinity of the wall demonstrate some deviation from planar shape. There is a tilted orientational ordering of the molecules which depends on the location of the molecule. It is shown that the diffusion coefficient of the benzene molecules is very small at the conditions we report here. © 2015 Wiley Periodicals, Inc.

The behavior of benzene confined in single wall carbon nanotube is studied by means of molecular dynamics simulation. Structural and dynamical properties are considered. The density and the temperature effects on the structure and diffusion of benzene are considered.

The key role of the molecular orbitals in describing electron transfer processes is put in evidence for the intervalence charge transfer (IVCT) of a synthetic nonheme binuclear mixed-valence Fe^{3+}/Fe^{2+} compound. The electronic reorganization induced by the IVCT can be quantified by controlling the adaptation of the molecular orbitals to the charge transfer process. We evaluate the transition energy and its polarization effects on the molecular orbitals by means of *ab initio* calculations. The resulting energetic profile of the IVCT shows strong similarities to the Marcus' model, suggesting a response behaviour of the ensemble of electrons analogue to that of the solvent. We quantify the extent of the electronic reorganization induced by the IVCT process to be 11.74 eV, a very large effect that induces the crossing of states reducing the total energy of the transfer to 0.89 eV. © 2015 Wiley Periodicals, Inc.

The electronic reorganization induced by the intervalence charge transfer of a synthetic nonheme binuclear mixed-valence Fe^{3+}/Fe^{2+} complex determines the energy cost of the electron transfer. The largest electronic reorganization occurs in the pyrimidinic N atoms and the bridge O of the first coordination shell, being weaker in the metal centres. The adaptation of the molecular orbitals to the electron transfer is sufficient to inverse the spectroscopy and generate a metastable electron transfer state.

QuickFF is a software package to derive accurate force fields for isolated and complex molecular systems in a quick and easy manner. Apart from its general applicability, the program has been designed to generate force fields for metal-organic frameworks in an automated fashion. The force field parameters for the covalent interaction are derived from *ab initio* data. The mathematical expression of the covalent energy is kept simple to ensure robustness and to avoid fitting deficiencies as much as possible. The user needs to produce an equilibrium structure and a Hessian matrix for one or more building units. Afterward, a force field is generated for the system using a three-step method implemented in QuickFF. The first two steps of the methodology are designed to minimize correlations among the force field parameters. In the last step, the parameters are refined by imposing the force field parameters to reproduce the *ab initio* Hessian matrix in Cartesian coordinate space as accurate as possible. The method is applied on a set of 1000 organic molecules to show the easiness of the software protocol. To illustrate its application to metal-organic frameworks (MOFs), QuickFF is used to determine force fields for MIL-53(Al) and MOF-5. For both materials, accurate force fields were already generated in literature but they requested a lot of manual interventions. QuickFF is a tool that can easily be used by anyone with a basic knowledge of performing *ab initio* calculations. As a result, accurate force fields are generated with minimal effort. © 2015 Wiley Periodicals, Inc.

QuickFF is a software package to derive accurate force fields for isolated and complex molecular systems in a quick and easy manner. Apart from its general applicability, the program has been designed to generate force fields for metal-organic frameworks in an automated fashion. The force field parameters for the covalent terms are derived from *ab initio* data. As a result, accurate force fields are generated with minimal effort.

Adaptation of improved virtual orbitals (IVOs) in state-specific multireference perturbation theory using Møller–Plesset multipartitioning of the Hamiltonian (IVO-SSMRPT) is examined in which the IVO-complete active space configuration interaction (CASCI) is used as an inexpensive alternative to the more involved CAS-self-consistent field (CASSCF) orbitals. Unlike the CASSCF approach, IVO-CASCI does not bear tedious and costly iterations beyond those in the initial SCF calculation. The IVO-SSMRPT is intruder-free, and explicitly size-extensive. In the present preliminary study, the IVO-SSMRPT method which relies on a small reference space is applied to study potential energy surfaces (PES) of the ground state of challenging, multiconfigurational F_{2}, Be_{2}, and N_{2} molecules. These systems provide a serious challenge to any *ab initio* methodology due to the presence of an intricate interplay of nondynamical and dynamical correlations to the entire PES. The quality of the computed PES has been judged by extracting spectroscopic parameters and vibrational levels. The reported results illustrate that the IVO-SSMRPT method has a potential to yield accuracies as good as the CASSCF-SSMRPT one with reduced computational labor. Even with small reference spaces, our estimates demonstrate a good agreement with the available experimental values, and some benchmark computations. The blend of accuracy and low computational cost of IVO-SSMRPT should deserve future attention for the accurate treatment of electronic states of small to large molecular systems for which the wavefunction is characterized by various configurations. © 2015 Wiley Periodicals, Inc.

Improved virtual orbital-complete active space configuration interaction-based state-specific multireference perturbation theory in the frame of Rayleigh–Schrödinger perturbative expansion has been used to investigate the spectroscopic constants and vibrational spectrum of F_{2}, Be_{2}, and N_{2} through the computation of dissociation energy surfaces.

The prevalence of Mg^{2+} ions in biology and their essential role in nucleic acid structure and function has motivated the development of various Mg^{2+} ion models for use in molecular simulations. Currently, the most widely used models in biomolecular simulations represent a nonbonded metal ion as an ion-centered point charge surrounded by a nonelectrostatic pairwise potential that takes into account dispersion interactions and exchange effects that give rise to the ion's excluded volume. One strategy toward developing improved models for biomolecular simulations is to first identify a Mg^{2+} model that is consistent with the simulation force fields that closely reproduces a range of properties in aqueous solution, and then, in a second step, balance the ion–water and ion–solute interactions by tuning parameters in a pairwise fashion where necessary. The present work addresses the first step in which we compare 17 different nonbonded single-site Mg^{2+} ion models with respect to their ability to simultaneously reproduce structural, thermodynamic, kinetic and mass transport properties in aqueous solution. None of the models based on a 12-6 nonelectrostatic nonbonded potential was able to reproduce the experimental radial distribution function, solvation free energy, exchange barrier and diffusion constant. The models based on a 12-6-4 potential offered improvement, and one model in particular, in conjunction with the SPC/E water model, performed exceptionally well for all properties. The results reported here establish useful benchmark calculations for Mg^{2+} ion models that provide insight into the origin of the behavior in aqueous solution, and may aid in the development of next-generation models that target specific binding sites in biomolecules. © 2015 Wiley Periodicals, Inc.

Mg^{2+} ions are essential for nucleic acid structure and function and this has motivated the development of several Mg^{2+} models for use in molecular simulations. As a first step in developing improved Mg^{2+} models for biomolecular simulations, we focus on the ability to which 17 different pairwise potential Mg^{2+} models, which belong to the most mature force fields for modeling nucleic acid dynamics, can simultaneously reproduce structural, thermodynamic, kinetic and mass transport properties in aqueous solution. These represent a balanced set of solution properties that serve as a useful departure point from which robust models for molecular dynamics simulations of biological processes can be developed by tuning pairwise interaction parameters.

The reduction and oxidation properties of four nitrocompounds (trinitrotoluene [TNT], 2,4-dinitrotoluene, 2,4-dinitroanisole, and 5-nitro-2,4-dihydro-3*H*-1,2,4-triazol-3-one [NTO]) dissolved in water as compared with the same properties for compounds adsorbed on a silica surface were studied. To consider the influence of adsorption, cluster models were developed at the M05/tzvp level. A hydroxylated silica (001) surface was chosen to represent a key component of soil. The PCM(Pauling) and SMD solvation models were used to model water bulk influence. The following properties were analyzed: electron affinity, ionization potential, reduction Gibbs free energy, oxidation Gibbs free energy, and reduction and oxidation potentials. It was found that adsorption and solvation decrease gas phase electron affinity, ionization potential, and Gibbs free energy of reduction and oxidation, and thus, promote redox transformation of nitrocompounds. However, in case of solvation, the changes are more significant than for adsorption. This means that nitrocompounds dissolved in water are easier to transform by reduction or oxidation than adsorbed ones. Among the considered compounds, TNT was found to be the most reactive in an electron attachment process and the least reactive for an electron detachment transformation. During ionization, a deprotonation of adsorbed NTO was found to occur. © 2015 Wiley Periodicals, Inc.

Reduction and oxidation properties of trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4-dinitroanisole (DNAN), and 5-nitro-2,4-dihydro-3*H*-1,2,4-triazol-3-one (NTO) were studied in gas phase, in water, and adsorbed on a silica surface state. It was found that adsorption and solvation promote redox transformation of nitrocompounds. Nitrocompounds dissolved in water are easier to transform than adsorbed ones. Reactivity in an electron attachment and electron detachment processes increases in the rows: DNT < DNAN ≈ NTO < TNT and TNT < DNT < DNAN < NTO, respectively.

Procedure for deriving Wyckoff positions for nanowires (NWs) and nanotubes (NTs) from Wyckoff positions of ambient space group is described. It is proposed how to use SITESYM code available on Bilbao Crystallographic Server to calculate representations induced from orbit stabilizers for 1-periodic groups. This procedure is demonstrated on the example of TiO_{2} rutile-based NWs. General analytic expressions for Line group representations induced from irreps of their orbit stabilizers are obtained. This approach presupposes the use of the standard (crystallographic) factorization of Line groups. Computer construction of orbits and induced representations can be efficiently implemented and the corresponding computer code SITESYML, which can be considered as a certain elaboration of the existing code SITESYM is written. The application of the code is demonstrated on the example of TiO_{2} anatase-based NTs with the rectangular and hexagonal morphology. © 2015 Wiley Periodicals, Inc.

General approach to the phonon symmetry analysis for nanowires and nanotubes is outlined. It is illustrated on the example of TiO_{2} rutile-based nanorods and TiO_{2} anatase-based nanotubes with the hexagonal and rectangular morphology, respectively. The number and symmetry of Infrared active, Raman active, and silent modes is found, which is important for the vibrational spectra interpretations of the systems in consideration. There are four acoustic modes with zero frequencies for **k** = 0: three longitudinal acoustic and one twisting.

The halogen bonded complexes between six carbonyl bases and molecular chlorine are investigated theoretically. The interaction energies calculated at the CCSD(T)/aug-cc-pVTZ level range between −1.61 and −3.50 kcal mol^{−1}. These energies are related to the ionization potential, proton affinity, and also to the most negative values (*V*_{s,min}) on the electrostatic potential surface of the carbonyl bases. A symmetry adapted perturbation theory decomposition of the energies has been performed. The interaction results in an elongation of the ClCl bond and a contraction of the CF and CH bonds accompanied by a blue shift of the ν(CH) vibrations. The properties of the Cl_{2} molecules are discussed as a function of the σ*(ClCl) occupation, the hybridization, and the occupation of the Rydberg orbitals of the two chlorine atoms. Our calculations predict a large enhancement of the infrared and Raman intensities of the ν(ClCl) vibration on going from isolated to complexed Cl_{2}. © 2015 Wiley Periodicals, Inc.

The halogen-bonded complexes between six carbonyl bases and molecular chlorine are investigated theoretically. The study includes the optimized geometries and the interaction energies along with an extended natural bond orbital analysis. The interaction energies calculated at the CCSD(T)/aug-cc-pVTZ level range between −1.61 and −3.50 kcal mol^{−1}. These energies are related to the ionization potential and the proton affinity of the carbonyl bases.

The dynamics of complex systems with many degrees of freedom can be analyzed by projecting it onto one or few coordinates (collective variables). The dynamics is often described then as diffusion on a free energy landscape associated with the coordinates. Fep1d is a script for the analysis of such one-dimensional coordinates. The script allows one to construct conventional and cut-based free energy profiles, to assess the optimality of a reaction coordinate, to inspect whether the dynamics projected on the coordinate is diffusive, to transform (rescale) the reaction coordinate to more convenient ones, and to compute such quantities as the mean first passage time, the transition path times, the coordinate dependent diffusion coefficient, and so forth. Here, we describe the implemented functionality together with the underlying theoretical framework. © 2015 Wiley Periodicals, Inc.

Multidimensional dynamical processes can be analyzed by projecting them onto one or few coordinates (collective variables). The dynamics is often described then as diffusion on a free energy landscape associated with the coordinates. Fep1d is a script which can be used to answer questions appearing during such an analysis. In particular, the determination of the associated free energy profile and the diffusion coefficient and establishing whether the used coordinate is optimal.

In this study, we use a very simple scheme to achieve range separation of a total exchange–correlation functional. We have utilized this methodology to combine a short-range pure density functional theory (DFT) functional with a corresponding long-range pure DFT, leading to a “Range-separated eXchange–Correlation” (RXC) scheme. By examining the performance of a range of standard exchange–correlation functionals for prototypical short- and long-range properties, we have chosen B-LYP as the short-range functional and PBE-B95 as the long-range counterpart. The results of our testing using a more diverse range of data sets show that, for properties that we deem to be short-range in nature, the performance of this prescribed RXC-DFT protocol does resemble that of B-LYP in most cases, and *vice versa*. Thus, this RXC-DFT protocol already provides meaningful numerical results. Furthermore, we envisage that the general RXC scheme can be easily implemented in computational chemistry software packages. This study paves a way for further refinement of such a range-separation technique for the development of better performing DFT procedures. © 2015 Wiley Periodicals, Inc.

Range separation for the exchanged functional has contributed significantly to the advancement of DFT. A simple “Range-separated eXchange–Correlation” (RXC) scheme is used to divide a total exchange–correlation functional. For properties that are short-range in nature, the performance of the RXC-DFT protocol resembles that of the short-range component, and vice versa. The general RXC scheme can be easily implemented in computational chemistry software packages.

We investigate the accuracy of two-component Douglas–Kroll–Hess (DKH) methods in calculations of the nuclear volume term (≡ lnK_{nv}) in the isotope fractionation coefficient. lnK_{nv} is a main term in the chemical equilibrium constant for isotope exchange reactions in heavy element. Previous work based on the four-component method reasonably reproduced experimental lnK_{nv} values of uranium isotope exchange. In this work, we compared uranium reaction lnK_{nv} values obtained from the two-component and four-component methods. We find that both higher-order relativistic interactions and spin-orbit interactions are essential for quantitative description of lnK_{nv}. The best alternative is the infinite-order Douglas–Kroll–Hess method with infinite-order spin-orbit interactions for the one-electron term and atomic-mean-field spin-same-orbit interaction for the two-electron term (IODKH-IOSO-MFSO). This approach provides almost equivalent results for the four-component method, while being 30 times faster. The IODKH-IOSO-MFSO methodology should pave the way toward computing larger and more general molecules beyond the four-component method limits. © 2015 Wiley Periodicals, Inc.

Nuclear volume term is a main term in the chemical equilibrium constants of isotope fractionations with heavy-element isotopes. The nuclear volume term can be calculated by the four-component Dirac-Hartree-Fock method. In this work, various types of two-component quasi-relativistic methods are performed in an attempt to find alternatives to the time-consuming four-component method. One of the infinite-order Douglass-Kroll-Hess methods is found to be accurate, but 30 times faster than the four-component method.

Water is essential for the proper folding of proteins and the assembly of protein–protein/ligand complexes. How water regulates complex formation depends on the chemical and topological details of the interface. The dynamics of water in the interdomain region between an E3 ubiquitin ligase (MDM2) and three different peptides derived from the tumor suppressor protein p53 are studied using molecular dynamics. The peptides show bimodal distributions of interdomain water densities across a range of distances. The addition of a hydrocarbon chain to rigidify the peptides (in a process known as stapling) results in an increase in average hydrophobicity of the peptide–protein interface. Additionally, the hydrophobic staple shields a network of water molecules, kinetically stabilizing a water chain hydrogen-bonded between the peptide and MDM2. These properties could result in a decrease in the energy barrier associated with dehydrating the peptide–protein interface, thereby regulating the kinetics of peptide binding. © 2015 Wiley Periodicals, Inc.

Protein–peptide interfaces have nonuniform chemical properties and geometry, posing challenges to understanding the driving forces of hydrophobicity, particularly at atomic-level detail. The dynamics of water between an E3 ubiquitin ligase (MDM2) and peptides derived from the tumor suppressor protein p53 (including a hydrocarbon “stapled” one) are studied using molecular dynamics. The interdomain densities show two-state behavior, and the relative fraction of wet and dry states is used to compare the extent of hydrophobicity.

Recently, diketopyrrolopyrrole (DPP)-based materials have attracted much interest due to their promising performance as a subunit in organic field effect transistors. Using density functional theory and charge-transport models, we investigated the electronic structure and microscopic charge transport properties of the cyanated bithiophene-functionalized DPP molecule (compound **1**). First, we analyzed in detail the partition of the total relaxation (polaron) energy into the contributions from each vibrational mode and the influence of bond-parameter variations on the local electron–vibration coupling of compound **1**, which well explains the effects of different functional groups on internal reorganization energy (*λ*). Then, we investigated the structural and electronic properties of compound **1** in its isolated molecular state and in the solid state form, and further simulated the angular resolution anisotropic mobility for both electron- and hole-transport using two different simulation methods: (i) the mobility orientation function proposed in our previous studies (method 1); and (ii) the master equation approach (method 2). The calculated electron-transfer mobility (0.00003–0.784 cm^{2} V^{−1} s^{−1} from method 1 and 0.02–2.26 cm^{2} V^{−1} s^{−1} from method 2) matched reasonably with the experimentally reported value (0.07–0.55 cm^{2} V^{−1} s^{−1}). To the best of our knowledge, this is the first time that the transport parameters of compound **1** were calculated in the context of band model and hopping models, and both calculation results suggest that the intrinsic hole mobility is higher than the corresponding intrinsic electron mobility. Our calculation results here will be instructive to further explore the potential of other higher DPP-containing quinoidal small molecules. © 2015 Wiley Periodicals, Inc.

The electronic structures and microscopic charge-transport properties of a diketopyrrolopyrrole-based material (compound **1**) were investigated using density functional theory and charge-transport models. It is the first time that the transport parameters of compound **1** were calculated in the context of band model and hopping models. Our investigations here, provide guidance for the understanding of the structure–function relationship and intermolecular charge-transport behaviors, and are instructive to further explore the potential of other higher diketopyrrolopyrrole-containing molecules.

In nanopore force spectroscopy (NFS) a charged polymer is threaded through a channel of molecular dimensions. When an electric field is applied across the insulating membrane, the ionic current through the nanopore reports on polymer translocation, unzipping, dissociation, and so forth. We present a new model that can be applied in molecular dynamics simulations of NFS. Although simplified, it does reproduce experimental trends and all-atom simulations. The scaled conductivities in bulk solution are consistent with experimental results for NaCl for a wide range of electrolyte concentrations and temperatures. The dependence of the ionic current through a nanopore on the applied voltage is symmetric and, in the voltage range used in experiments (up to 2 V), linear and in good agreement with experimental data. The thermal stability and geometry of DNA is well represented. The model was applied to simulations of DNA hairpin unzipping in nanopores. The results are in good agreement with all-atom simulations: the scaled translocation times and unzipping sequence are similar. © 2015 Wiley Periodicals, Inc.

In nanopore force spectroscopy (NFS), a charged polymer is threaded through a channel of molecular dimensions. When an electric field is applied across the insulating membrane, the ionic current through the nanopore reports on polymer translocation, unzipping, dissociation, and so forth. A new model is presented that can be applied in molecular dynamics simulations of NFS. Although simplified, it does reproduce experimental trends and all-atom simulations. The model was applied to simulations of DNA hairpin unzipping in nanopores.

We revisit the singlet–triplet energy gap (Δ*E*_{ST}) of silicon trimer and evaluate the gaps of its derivatives by attachment of a cation (H^{+}, Li^{+}, Na^{+}, and K^{+}) using the wavefunction-based methods including the composite G4, coupled-cluster theory CCSD(T)/CBS, CCSDT and CCSDTQ, and CASSCF/CASPT2 (for Si_{3}) computations. Both ^{1}A_{1} and ^{3}
states of Si_{3} are determined to be degenerate. An intersystem crossing between both states appears to be possible at a point having an apex bond angle of around *α* = 68 ± 2° which is 16 ± 4 kJ/mol above the ground state. The proton, Li^{+} and Na^{+} cations tend to favor the low-spin state, whereas the K^{+} cation favors the high-spin state. However, they do not modify significantly the Δ*E*_{ST}. The proton affinity of silicon trimer is determined as PA(Si_{3}) = 830 ± 4 kJ/mol at 298 K. The metal cation affinities are also predicted to be LiCA(Si_{3}) = 108 ± 8 kJ/mol, NaCA(Si_{3}) = 79 ± 8 kJ/mol and KCA(Si_{3}) = 44 ± 8 kJ/mol. The chemical bonding is probed using the electron localization function, and ring current analyses show that the singlet three-membered ring Si_{3} is, at most, nonaromatic. Attachment of the proton and Li^{+} cation renders it anti-aromatic. © 2015 Wiley Periodicals, Inc.

Both ^{1}A_{1} and ^{3}
states of Si_{3} are degenerate. The H^{+}, Li^{+}, and Na^{+} cations favor the singlet state, whereas K^{+} favors the triplet. Some thermochemical parameters are predicted: PA(Si_{3}) = 830 ± 4, LiCA(Si_{3}) = 108 ± 8, NaCA(Si_{3}) = 79 ± 8, and KCA(Si_{3}) = 44 ± 8 kJ/mol. The ring current shows that the singlet three-membered Si_{3} ring is, at most, nonaromatic. Attachment of H^{+} and Li^{+} renders it anti-aromatic.

Binding energies of ion triplets formed in ionic liquids by Li^{+} with two anions have been studied using quantum-chemical calculations with implicit and explicit solvent supplemented by molecular dynamics (MD) simulations. Explicit solvent approach confirms variation of solute-ionic liquid interactions at distances up to 2 nm, resulting from structure of solvation shells induced by electric field of the solute. Binding energies computed in explicit solvent and from the polarizable continuum model approach differ largely, even in sign, but relative values generally agree between these two models. Stabilities of ion triplets obtained in quantum-chemical calculations for some systems disagree with MD results; the discrepancy is attributed to the difference between static optimized geometries used in quantum chemical modeling and dynamic structures of triplets in MD simulations. © 2015 Wiley Periodicals, Inc.

Ion triplets [LiAn1An2]^{–} in five ionic liquids were investigated through Molecular Dynamics simulations and quantum-chemical calculations in continuous or explicit solvent. The relative binding energies of triplets obtained from the two solvent models were in general agreement.

We introduce a general procedure to construct a set of one-electron functions in chemical bonding theory, which remain physically sound both for correlated and noncorrelated electronic structure descriptions. These functions, which we call natural adaptive orbitals, decompose the *n*-center bonding indices used in real space theories of the chemical bond into one-electron contributions. For the *n* = 1 case, they coincide with the domain natural orbitals used in domain-averaged Fermi hole analyses. We examine their interpretation in the two-center case, and show how they behave and evolve in simple cases. Orbital pictures obtained through this technique converge onto the chemist's molecular orbital toolbox if electron correlation may be ignored, and provide new insight if it may not. © 2015 Wiley Periodicals, Inc.

A hierarchical set of one-electron functions called natural adaptive orbitals is introduced. *n*-center NAdOs decompose real space *n*-center bonding indices into one-electron contributions. NAdOs maintain their meaning both for correlated and noncorrelated descriptions.

The conformational samplings are indispensible for obtaining reliable canonical ensembles, which provide statistical averages of physical quantities such as free energies. However, the samplings of vast conformational space of biomacromolecules by conventional molecular dynamics (MD) simulations might be insufficient, due to their inadequate accessible time-scales for investigating biological functions. Therefore, the development of methodologies for enhancing the conformational sampling of biomacromolecules still remains as a challenging issue in computational biology. To tackle this problem, we newly propose an efficient conformational search method, which is referred as TaBoo SeArch (TBSA) algorithm. In TBSA, an inverse energy histogram is used to select seeds for the conformational resampling so that states with high frequencies are inhibited, while states with low frequencies are efficiently sampled to explore the unvisited conformational space. As a demonstration, TBSA was applied to the folding of a mini-protein, chignolin, and automatically sampled the native structure (C_{α} root mean square deviation < 1.0 Å) with nanosecond order computational costs started from a completely extended structure, although a long-time 1-µs normal MD simulation failed to sample the native structure. Furthermore, a multiscale free energy landscape method based on the conformational sampling of TBSA were quantitatively evaluated through free energy calculations with both implicit and explicit solvent models, which enable us to find several metastable states on the folding landscape. © 2015 Wiley Periodicals, Inc.

An enhanced conformational search method referred as TaBoo SeArch (TBSA) algorithm is proposed. In TBSA, an inverse energy histogram is used to select seeds for the conformational resampling so that states with high frequencies are inhibited. As a demonstration, TBSA was applied to the folding of chignolin and automatically sampled the native structure with nanosecond order computational costs, although a long-time 1-µs normal MD simulation failed to sample the native structure.

Despite the relatively small size of molecular bromine and iodine, the physicochemical behavior in different solvents is not yet fully understood, in particular when excited-state properties are sought. In this work, we investigate isolated halogen molecules trapped in clathrate hydrate cages. Relativistic supermolecular calculations reveal that the environment shift to the excitation energies of the (nondegenerate) states and lie within a spread of 0.05 eV, respectively, suggesting that environment shifts can be estimated with scalar-relativistic treatments. As even scalar-relativistic calculations are problematic for excited-state calculations for clathrates with growing size and basis sets, we have applied the subsystem-based scheme frozen-density embedding, which avoids a supermolecular treatment. This allows for the calculation of excited states for extended clusters with coupled-cluster methods and basis sets of triple-zeta quality with additional diffuse functions mandatory for excited-state properties, as well as a facile treatment at scalar-relativistic exact two-component level of theory for the heavy atoms bromine and iodine. This simple approach yields scalar-relativistic estimates for solvatochromic shifts introduced by the clathrate cages. © 2015 Wiley Periodicals, Inc.

Solvatochromic shifts are estimated for molecular bromine and iodine trapped in selected clathrate hydrate cages using frozen-density embedding, allowing for the combination of scalar-relativistic and nonrelativistic methods for heavy halogens and light water molecules, respectively.

A density functional theory (DFT) study was performed to elucidate the mechanism for the [5 + 1] benzannulation of nitroethane and α-alkenoyl ketene-(*S,S*)-acetals. The calculation results are consistent with experimental findings, showing that the reaction proceeds via deprotonation of nitroethane, nucleophilic addition, intramolecular cyclization, elimination of HNO_{2}, and the keto-enol tautomerization sequence. It was disclosed that N,N-dimethylformamide (DMF) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) act as not only solvent and nonnucleophilic base, respectively, but also catalysts in the reaction by stabilizing the transition states (TSs) and intermediates via intermolecular hydrogen bonds and electrostatic interactions. Besides, the effective orbital interaction of the reaction site in TS also contributes to the intramolecular cyclization step. The new mechanistic insights obtained by DFT calculations highlight that the hydrogen bonds and electrostatic interactions are key factors for the [5 + 1] benzannulation of nitroethane and α-alkenoyl ketene-(*S,S*)-acetals. © 2015 Wiley Periodicals, Inc.

The multieffects of DMF and DBU on the [5 + 1] Benzannulation of Nitroethane and α-alkenoyl ketene-(*S,S*)-acetals are investigated by the DFT calculations under unassisted, DBU assisted, and DBU with DMF cocatalyzed conditions. The calculated results suggest that DMF and DBU act as not only solvent and non-nucleophilic base, respectively but also catalysts in the reaction by stabilizing the transition states and intermediates via intermolecular hydrogen bonds and electrostatic interactions.

The interaction between single-walled carbon nanotubes (SWNTs) and graphene were studied with first-principles calculations. Both SWNTs and single-layer graphene (SLG) or double-layer graphene (DLG) display more remarkable deformations with the increase of SWNT diameter, which implies a stronger interaction between SWNTs and graphene. Besides, in DLG, deformation of the upper-layer graphene is less than in SLG. Zigzag SWNTs show stronger interactions with SLG than armchair SWNTs, whereas the order is reversed for DLG, which can be interpreted by the mechanical properties of SWNTs and graphene. Density of states and band structures were also studied, and it was found that the interaction between a SWNT and graphene is not strong enough to bring about obvious influence on the electronic structures of SWNTs. © 2015 Wiley Periodicals, Inc.

First-principles calculations were performed to investigate the interaction between single-walled carbon nanotubes (SWNTs) and graphene. Zigzag SWNTs show stronger interactions with SLG than armchair SWNTs of similar diameters, whereas armchair SWNTs display stronger interactions with DLG than zigzag SWNTs, which can be interpreted by the mechanical properties of SWNTs and graphene.

Current density plots of closed-shell intermolecular HH interactions characterized by a bond critical point (BCP) show two vortices separated by a saddle, a pattern which allows for a clear definition of a pair current strength. This HH current strength turns out to be roughly related to the potential energy density at the BCP and then to the dissociation energy. The same pattern is also recognizable, at least for an azimuthal orientation of a field perpendicular to the HH line, for the intramolecular interactions previously investigated to propose the HH bonding. In the case of the H atoms of the bay region of polycyclic aromatic hydrocarbons, the current of the HH delocalized diatropic vortex gives a quantitative indication of stabilization; however, on rotation of the field and the subsequent onset of a bay-delocalized paratropic vortex (a typical signature of antiaromaticity), the diatropic vortex can be reshaped or it can even disappear, consistently with its smallness, and thus showing the effect of other more relevant interactions. © 2015 Wiley Periodicals, Inc.

Hydrogen atoms involved in HH bonding are embraced by a small delocalized diatropic current, which can be used to assess the stabilizing character of their interaction.

Although electronic and magnetic circular dichroism (ECD, MCD) spectra reveal valuable details about molecular geometry and electronic structure, quantum-chemical simulations significantly facilitate their interpretation. However, the simulated results may depend on the choice of coordinate origin. Previously (Štěpánek and Bouř, J. Comput. Chem. 2013, 34, 1531), the sum-over-states (SOS) methodology was found useful for efficient MCD computations. Approximate wave functions were “resolved” using time-dependent density functional theory, and the origin-dependence was avoided by placing the origin to the center of mass of the investigated molecule. In this study, a more elegant way is proposed, based on the localized orbital/local origin (LORG) formalism, and a similar approach is also applied to generate ECD intensities. The LORG-like approach yields fully origin-independent ECD and MCD spectra. The results thus indicate that the computationally relatively cheap SOS simulations open a new way of modeling molecular properties, including those involving the origin-dependent magnetic dipole moment operator. © 2015 Wiley Periodicals, Inc.

The sum over state method using states from the time-dependent density functional theory is convenient for fast simulations of molecular magnetic circular dichroism spectra. In the original formulation, the molecule was kept at the coordinate origin to obtain reproducible results. In this work, an alternative way is explored, providing fully origin-independent natural electronic and magnetic circular dichroic intensities.

Using the accurate Wn-F12 thermochemical protocols, Amir Karton and Lars Goerigk show on page 622 (DOI: 10.1002/jcc.23837) that the widely used and popular CBS-QB3 composite method produces unusually large deviations for pericyclic reaction barrier heights. This unexpected finding has a significant impact on benchmark studies carried out for the assessment of density-functional-theory methods. Several related key issues are discussed in this context. These examples are a reminder to be cautious in the application of CBS-type composite methods in similar situations.

The image depicts the efficacy of Unitary Group Adapted State-Specific Multireference Perturbation Theory (UGA-SSMRPT2) for computing in an intruder-free manner the potential energy surface of “difficult” molecular states requiring a balanced inclusion of static and dynamic correlation. On page 670 (DOI: 10.1002/jcc.23851), Avijit Sen, Sangita Sen, Pradipta Kumar Samanta, and Debashis Mukherjee report the working equations are simple and incur low computational cost, yet are founded on sound physics involving a multireference starting function (CASSCF) and inclusion of dynamical correlation via perturbation, while maintaining the size extensivity and size-consistency of the energy. The perturbative wave function is a spin-eigenfunction due to the UGA formulation of the theory.

The generalized Born model in the Onufriev, Bashford, and Case (Onufriev et al., Proteins: Struct Funct Genet 2004, 55, 383) implementation has emerged as one of the best compromises between accuracy and speed of computation. For simulations of nucleic acids, however, a number of issues should be addressed: (1) the generalized Born model is based on a linear model and the linearization of the reference Poisson–Boltmann equation may be questioned for highly charged systems as nucleic acids; (2) although much attention has been given to potentials, solvation forces could be much less sensitive to linearization than the potentials; and (3) the accuracy of the Onufriev–Bashford–Case (OBC) model for nucleic acids depends on fine tuning of parameters. Here, we show that the linearization of the Poisson Boltzmann equation has mild effects on computed forces, and that with optimal choice of the OBC model parameters, solvation forces, essential for molecular dynamics simulations, agree well with those computed using the reference Poisson–Boltzmann model. © 2015 Wiley Periodicals, Inc.

The generalized Born model in the Onufriev, Bashford, and Case (OBC) implementation has emerged as one of the best compromises between accuracy and speed of computation. The linearization of the Poisson–Boltmann equation is shown to have mild effects on computed forces. With optimal choice of the OBC model parameters, the solvation forces, essential for molecular dynamics simulations, agree well with those computed using the reference Poisson–Boltzmann model.

Developing a better understanding of the bulk properties of ionic liquids requires accurate measurements of the underlying molecular properties that help to determine the bulk behavior. Two computational methods are used in this work: second-order perturbation theory (MP2) and completely renormalized coupled cluster theory [CR-CC(2,3)], to calculate the proton affinity and ionization potential of a set of anions that are of interest for use in protic, energetic ionic liquids. Compared with experimental values, both methods predict similarly accurate proton affinities, but CR-CC(2,3) predicts significantly more accurate ionization potentials. It is concluded that more time intensive methods like CR-CC(2,3) are required in calculations involving open shell states like the ionization potential. © 2015 Wiley Periodicals, Inc.

A comparison of the accuracy of MP2 and the high level coupled cluster method [CR-CC(2,3)] in predicting ionization potential and proton affinity of anions is made. The results show an increase in accuracy using CR-CC(2,3) for ionization potentials over MP2, but no significant difference in accuracy for proton affinities.

Reaction path finding and transition state (TS) searching are important tasks in computational chemistry. Methods that seek to optimize an evenly distributed set of structures to represent a chemical reaction path are known as double-ended string methods. Such methods can be highly reliable because the endpoints of the string are fixed, which effectively lowers the dimensionality of the reaction path search. String methods, however, require that the reactant and product structures are known beforehand, which limits their ability for systematic exploration of reactive steps. In this article, a single-ended growing string method (GSM) is introduced which allows for reaction path searches starting from a single structure. The method works by sequentially adding nodes along coordinates that drive bonds, angles, and/or torsions to a desired reactive outcome. After the string is grown and an approximate reaction path through the TS is found, string optimization commences and the exact TS is located along with the reaction path. Fast convergence of the string is achieved through use of internal coordinates and eigenvector optimization schemes combined with Hessian estimates. Comparison to the double-ended GSM shows that single-ended method can be even more computationally efficient than the already rapid double-ended method. Examples, including transition metal reactivity and a systematic, automated search for unknown reactivity, demonstrate the efficacy of the new method. This automated reaction search is able to find 165 reaction paths from 333 searches for the reaction of NH_{3}BH_{3} and (LiH)_{4}, all without guidance from user intuition. © 2015 Wiley Periodicals, Inc.

Single-ended transition state findings are now possible in the growing string method, which allows a simultaneous search for reaction paths and transition states without knowledge of the product structure. This new method is shown to rapidly uncover detailed mechanistic information at a low cost and with low user effort.

The interplay between electrostatic and van der Waals (vdW) interactions in porphyrin-C_{60} dyads is still under debate despite its importance in influencing the structural characteristics of such complexes considered for various applications in molecular photovoltaics. In this article, we sample the conformational space of a porphyrin-C_{60} dyad using Car–Parrinello molecular dynamics simulations with and without empirical vdW corrections. Long-range vdW interactions, which are poorly described by the commonly used density functional theory functionals, prove to be essential for a proper dynamics of the dyad moieties. Inclusion of vdW corrections brings porphyrin and C_{60} close together in an orientation that is in agreement with experimental observations. The structural differences arising from the vdW corrections are shown to be significant for several properties and potentially less important for others. Additionally, our Mulliken population analysis reveals that contrary to the common belief, porphyrin is not the primary electron donating moiety for C_{60}. In the considered dyad, fullerene's affinity for electrons is primarily satisfied by charge transfer from the amide group of the linker. However, we show that in the absence of another suitable bound donor, C_{60} can withdraw electrons from porphyrin if it is sufficiently close. © 2015 Wiley Periodicals, Inc.

The interplay between electrostatic and van der Waals (vdW) interactions in the formation of porphyrin-fullerene (Ph–C_{60}) dimers is still under debate despite its importance in determining the structural characteristics of these complexes, which are extensively as artificial photosynthesis centers in organic solar cells. Car–Parrinello molecular dynamics (CPMD) simulations with and without empirical vdW corrections are used to study the geometry and physical properties of a Ph–C_{60} dyad.

Accurate barrier heights are obtained for the 26 pericyclic reactions in the BHPERI dataset by means of the high-level W*n*-F12 thermochemical protocols. Very often, the complete basis set (CBS)-type composite methods are used in similar situations, but herein it is shown that they in fact result in surprisingly large errors with root mean square deviations (RMSDs) of about 2.5 kcal mol^{−1}. In comparison, other composite methods, particularly G4-type and estimated coupled cluster with singles, doubles, and quasiperturbative triple excitations [CCSD(T)/CBS] approaches, show deviations well below the chemical-accuracy threshold of 1 kcal mol^{−1}. With the exception of SCS-MP2 and the herein newly introduced MP3.5 approach, all other tested Møller-Plesset perturbative procedures give poor performance with RMSDs of up to 8.0 kcal mol^{−1}. The finding that CBS-type methods fail for barrier heights of these reactions is unexpected and it is particularly troublesome given that they are often used to obtain reference values for benchmark studies. Significant differences are identified in the interpretation and final ranking of density functional theory (DFT) methods when using the original CBS-QB3 rather than the new W*n*-F12 reference values for BHPERI. In particular, it is observed that the more accurate W*n*-F12 benchmark results in lower statistical errors for those methods that are generally considered to be robust and accurate. Two examples are the PW6B95-D3(BJ) hybrid-meta-general-gradient approximation and the PWPB95-D3(BJ) double-hybrid functionals, which result in the lowest RMSDs of the entire DFT study (1.3 and 1.0 kcal mol^{−1}, respectively). These results indicate that CBS-QB3 should be applied with caution in computational modeling and benchmark studies involving related systems. © 2015 Wiley Periodicals, Inc.

Using the accurate W*n*-F12 thermochemical protocols, it is shown that the widely used and popular CBS-QB3 composite method produces unusually large deviations for pericyclic reaction barrier heights. This unexpected finding has a significant impact on benchmark studies carried out for the assessment of density-functional-theory methods. Several related key issues are discussed in this context. These examples are a reminder to be cautious in the application of CBS-type composite methods in similar situations.

The implementation and validation of the adaptive buffered force (AdBF) quantum-mechanics/molecular-mechanics (QM/MM) method in two popular packages, CP2K and AMBER are presented. The implementations build on the existing QM/MM functionality in each code, extending it to allow for redefinition of the QM and MM regions during the simulation and reducing QM-MM interface errors by discarding forces near the boundary according to the buffered force-mixing approach. New adaptive thermostats, needed by force-mixing methods, are also implemented. Different variants of the method are benchmarked by simulating the structure of bulk water, water autoprotolysis in the presence of zinc and dimethyl-phosphate hydrolysis using various semiempirical Hamiltonians and density functional theory as the QM model. It is shown that with suitable parameters, based on force convergence tests, the AdBF QM/MM scheme can provide an accurate approximation of the structure in the dynamical QM region matching the corresponding fully QM simulations, as well as reproducing the correct energetics in all cases. Adaptive unbuffered force-mixing and adaptive conventional QM/MM methods also provide reasonable results for some systems, but are more likely to suffer from instabilities and inaccuracies. © 2015 Wiley Periodicals, Inc.

Implementations of an adaptive method for QM/MM simulations in the CP2K and AMBER packages are presented, making it straightforward to quantum mechanically describe not only the reacting species, but also a surrounding region of solvent, because the set of quantum atoms can be changed adaptively in the simulation. Geometries and free energy profiles are compared to those of full quantum mechanical simulations to show that the method is more robust than alternatives.

Translating local electro/nucleophilicities into the language of reactive sites is an appealing theoretical challenge that could be conducive to strengthen the collaborative dialogue between experimentalists and quantum chemists. The usual schemes for such condensation, relying on atomic charges, may however lead to important information loss, due to a sometimes inappropriate averaging of the reactivity anisotropy. In this article, we present instead an approach based on the dual descriptor Δ*f*, which aims at partitioning real space into nonoverlapping reactive domains that feature a constant Δ*f* sign. This strategy enables not only to identify the nucleo/electrophilic regions inside a molecule but also to quantify meaningful properties (mean value, volume, electron population…). Its interest is then illustrated on two specific chemical problems: the measure of σ-holes in the context of halogen bonds, and of the electrophilicity of organic carbocations, casting the light on the versatility of this method. © 2015 Wiley Periodicals, Inc.

Electrophilic and nucleophilic regions inside a molecule are delimited in real space and quantified using the dual descriptor. This partition scheme is applied to the reactivity of carbocations and to the prediction of the strength of halogen bonds.

The coordination of Cu^{+} at the T1 and T7 positions of the M7 ring of Cu-ZSM-5, and the interaction of NO with coordinated Cu^{+} were investigated by means of DFT/ONIOM calculations. The B3LYP, BLYP, PBE1PBE, PBE, M06, and M062X functionals with the def2-TZVP (def2-QZVP for Cu) basis set were used in the high-level part of ONIOM calculations, with the HF/3-21G, B3LYP/LANL2DZ, M06/LANL2DZ, and M062X/LANL2DZ methods in the low-level part. The ability of suitable combinations of the above methods to reproduce (i) the crystallographic structure of purely siliceous ZSM-5, (ii) the tendency of Cu^{+} to be twofold or fourfold coordinated by framework oxygen atoms of Cu-ZSM-5, and (iii) the interaction energy and the NO stretching frequency of adsorbed nitrogen oxide are discussed, showing that different results are obtained depending on the adopted computational approach. With reference to above properties, some considerations about the employment of the ONIOM approximations are also included. © 2015 Wiley Periodicals, Inc.

The coordination of Cu^{+} to the T1 and T7 sites of Cu-ZSM-5 was investigated. ONIOM-2 calculations were performed at the DFT level by the B3LYP, BLYP, PBE1PBE, PBE, M06, and M062X functionals with extended basis set. Cu^{+} coordination and the energetics of NO adsorption are affected by the functional choice. The computational approach to the low-level part of ONIOM-2 calculations is also discussed.

We present here a comprehensive account of the formulation and pilot applications of the second-order perturbative analogue of the recently proposed unitary group adapted state-specific multireference coupled cluster theory (UGA-SSMRCC), which we call as the UGA-SSMRPT2. We also discuss the essential similarities and differences between the UGA-SSMRPT2 and the allied SA-SSMRPT2. Our theory, like its parent UGA-SSMRCC formalism, is size-extensive. However, because of the noninvariance of the theory with respect to the transformation among the active orbitals, it requires the use of localized orbitals to ensure size-consistency. We have demonstrated the performance of the formalism with a set of pilot applications, exploring (a) the accuracy of the potential energy surface (PES) of a set of small prototypical difficult molecules in their various low-lying states, using natural, pseudocanonical and localized orbitals and compared the respective nonparallelity errors (NPE) and the mean average deviations (MAD) vis-a-vis the full CI results with the same basis; (b) the efficacy of localized active orbitals to ensure and demonstrate manifest size-consistency with respect to fragmentation. We found that natural orbitals lead to the best overall PES, as evidenced by the NPE and MAD values. The MRMP2 results for individual states and of the MCQDPT2 for multiple states displaying avoided curve crossings are uniformly poorer as compared with the UGA-SSMRPT2 results. The striking aspect of the size-consistency check is the complete insensitivity of the sum of fragment energies with given fragment spin-multiplicities, which are obtained as the asymptotic limit of super-molecules with different coupled spins. © 2015 Wiley Periodicals, Inc.

Diagrammatic depiction of the structure of the working equations for the cluster amplitudes
and
is presented. The shaded blocks are the composites, G, obtained by connecting the unperturbed Hamiltonian, *H*_{0}, and the cluster operators, *T _{μ}*, as well as the perturbation, V, for a given partitioning and when acting on a model function
. The block diagrams clearly indicate that the amplitudes of only the proportional G-blocks are added together.

Motivation: A cluster of strongly interacting ionization groups in protein molecules with irregular ionization behavior is suggestive for specific structure–function relationship. However, their computational treatment is unconventional (e.g., lack of convergence in naive self-consistent iterative algorithm). The stringent evaluation requires evaluation of Boltzmann averaged statistical mechanics sums and electrostatic energy estimation for each microstate. Summary: irGPU: Irregular strong interactions in proteins—a GPU solver is novel solution to a versatile problem in protein biophysics—atypical protonation behavior of coupled groups. The computational severity of the problem is alleviated by parallelization (via GPU kernels) which is applied for the electrostatic interaction evaluation (including explicit electrostatics via the fast multipole method) as well as statistical mechanics sums (partition function) estimation. Special attention is given to the ease of the service and encapsulation of theoretical details without sacrificing rigor of computational procedures. irGPU is not just a solution-in-principle but a promising practical application with potential to entice community into deeper understanding of principles governing biomolecule mechanisms. © 2015 Wiley Periodicals, Inc.

IrGPU.proton.Net combines both theoretical rigor and practical flavor to help scientists elicit subtle issues in biomolecule physics.