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.

The H_{2} physisorption on Ag_{N} (with *N* = 32, 108, 256, 500, and 864)/carbon nanotube (CNT; in armchair and zigzag structures with diameters between 0.54 and 2.98 nm) composites were studied by molecular dynamic simulation to investigate the effect of nanocluster size, diameter, and chirality of nanotube on the adsorption phenomena. The calculations indicate that the effects of nanocluster properties are more important than those of the nanotube, in such a way that increase of nanocluster size, decreases the H_{2} adsorption. Also, the diameter and chirality of CNTs have considerable influence on the adsorption phenomena. As the diameter of nanotube is increased, the amount of adsorption is decreased. Moreover, H_{2} molecules have more tendencies to those nanoclusters located on the armchair nanotubes than the zigzag ones. Another important result is the reversibility of H_{2} adsorption on these materials in which the structure of composite in vacuum and after reduction of H_{2} pressure to zero, is not changed, considerably. © 2015 Wiley Periodicals, Inc.

H_{2} adsorption on (Ag-nanocluster)/(single-walled carbon nanotube) composites are studied by molecular dynamics simulation to investigate effects of nanocluster size, diameter, and chirality of nanotube. The results show that increase of nanocluster size and nanotube diameter decreases adsorption. Also, H_{2} adsorbates have more tendencies to the nanoclusters located on nanotubes with armchair chirality. Moreover, the effect of nanocluster size is more important than chirality of nanotube.

A series of photoresponsive-group-containing nanorings hosts with 12∼14 Å in diameter is designed by introducing different number of azo groups as the structural composition units. And the host–guest interactions between fullerene C_{60} and those nanoring hosts were investigated theoretically at M06-2X/6-31G(d)//M06-L/MIDI! and wB97X-D/6-31G(d) levels. Analysis on geometrical characteristics and host–guest binding energies revealed that the designed nanoring molecule (labeled as **7**) which is composed by seven azo groups and seven phenyls is the most feasible host for encapsulation of C_{60} guest among all candidates. Moreover, inferring from the simulated UV-vis-NIR spectroscopy, the C_{60} guest could be facilely released from the cavity of the host **7** via configuration transformation between *trans*-form and *cis*-form of the host under the 563 nm photoirradiation. Additionally, the frontier orbital features, weak interaction regions, infrared, and NMR spectra of the **C _{60}@7** host–guest complex have also been investigated theoretically. © 2015 Wiley Periodicals, Inc.

A series of photoresponsive nanorings was designed by employing different numbers of azobenze groups as construction units of host molecules. The complexes formed with guest C_{60} and these hosts were investigated theoretically. Host **7**, which is composed by seven azo groups and seven phenyls, is the most feasible host molecule for the encapsulation of guest C_{60} among all candidates; the guest C_{60} would be facile released from the cavity of the host **7** by configuration transformation under the 563 nm photoirradiation.

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.

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, used 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.

This study probes the nature of noncovalent interactions, such as cation–π, metal ion–lone pair (M–LP), hydrogen bonding (HB), charge-assisted hydrogen bonding (CAHB), and π–π interactions, using energy decomposition schemes—density functional theory (DFT)–symmetry-adapted perturbation theory and reduced variational space. Among cation–π complexes, the polarization and electrostatic components are the major contributors to the interaction energy (IE) for metal ion–π complexes, while for onium ion–π complexes (
,
,
, and
) the dispersion component is prominent. For M–LP complexes, the electrostatic component contributes more to the IE except the dicationic metal ion complexes with H_{2}S and PH_{3} where the polarization component dominates. Although electrostatic component dominates for the HB and CAHB complexes, dispersion is predominant in π–π complexes.Copyright © 2015 Wiley Periodicals, Inc.

The nature of cation–π, metal ion–lone pair (M–LP), hydrogen bonding (HB), charge-assisted hydrogen bonding (CAHB), and π–π interactions, has been probed through energy decomposition schemes. Although there is a mix of electrostatic, polarization, and dispersion components in all noncovalent interactions, their nature can be contrasted by comparing and contrasting the percentage contributions of these three components.

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 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.

An understanding of structure–function relationships of membrane proteins continues to be a challenging problem, owing to the difficulty in obtaining their structures experimentally. This study suggests a method for modeling membrane protein structures that can be used to generate a reliable initial conformation prior to the use of other approaches for sampling conformations. It involves optimizing the orientation of hydrophilic residues so as to minimize unfavorable contacts with the hydrophobic tails of the lipid bilayer. Starting with the optimized initial conformation for three different proteins modeled based on this method, two independent approaches have been used for sampling the conformational space of the proteins. Both approaches are able to predict structures reasonably close to experimental structures, indicating that the initial structure enables the sampling of conformations that are close to the native structure. Possible improvements in the method for making it broadly applicable to helical membrane proteins are discussed. © 2015 Wiley Periodicals, Inc.

A method has been proposed for generating putative initial structural models of membrane proteins, which can be considered for further molecular dynamics simulations. The initial models developed for the proteins M2, BM2, and ErbB2 provide structures close to the experimental structures via two independent sampling schemes.

Two of the most challenging problems that scientists and researchers face when they want to experiment with new cutting-edge algorithms are the time-consuming for encoding and the difficulties for linking them with other technologies and devices. In that sense, this article introduces the artificial organic networks toolkit for LabVIEW™ (AON-TL) from the implementation point of view. The toolkit is based on the framework provided by the artificial organic networks technique, giving it the potential to add new algorithms in the future based on this technique. Moreover, the toolkit inherits both the rapid prototyping and the easy-to-use characteristics of the LabVIEW™ software (e.g., graphical programming, transparent usage of other softwares and devices, built-in programming event-driven for user interfaces), to make it simple for the end-user. In fact, the article describes the global architecture of the toolkit, with particular emphasis in the software implementation of the so-called artificial hydrocarbon networks algorithm. Lastly, the article includes two case studies for engineering purposes (i.e., sensor characterization) and chemistry applications (i.e., blood–brain barrier partitioning data model) to show the usage of the toolkit and the potential scalability of the artificial organic networks technique. © 2015 Wiley Periodicals, Inc.

This article reviews the development process of the Artificial Organic Networks Toolkit, a graphical software package that implements the machine learning technique so-called artificial organic networks which it is inspired on chemical organic compounds. In addition, this work presents two practical case studies (sensor characterization and blood–brain barrier partitioning model) to show the usage of the toolkit.

Noncovalent interactions, such as hydrogen bonds and halogen bonds, are frequently used in drug designing and crystal engineering. Recently, a novel noncovalent pnicogen bonds have been identified as an important driving force in crystal structures with similar bonding mechanisms as hydrogen bond and halogen bond. Although the pnicogen bond is highly anisotropic, the pnicogen bond angles range from 160° to 180° due to the complicated substituent effects. To understand the anisotropic characters of pnicogen bond, a modification of the polarizable ellipsoidal force field (PEff) model previously used to define halogen bonds was proposed in this work. The potential energy surfaces (PESs) of mono- and polysubstituted PH_{3}–NH_{3} complexes were calculated at CCSD(T), MP2, and density functional theory levels and were used to examine the modified PEff model. The results indicate that the modified PEff model can precisely characterize pnicogen bond. The root mean squared error of PES obtained with PEff model is less than 0.5 kcal/mol, compared with MP2 results. In addition, the modified PEff model may be applied to other noncovalent bond interactions, which is important to understand the role of intermolecular interactions in the self-assembly structures. © 2015 Wiley Periodicals, Inc.

A modification of the polarizable ellipsoidal force field (PEff) model was proposed to understand the anisotropic characters of pnicogen bonds. The results indicate that the modified PEff model can precisely characterize pnicogen bonds. The root mean squared error between PESs obtained with PEff and MP2 models is less than 0.5 kcal/mol. This model may be applied to other noncovalent bond interactions to understand the role of anisotropic intermolecular interactions.

Lanthanide trihalide molecules LnX_{3} (X = F, Cl, Br, I) were quantum chemically investigated, in particular detail for Ln = Lu (lutetium). We applied density functional theory (DFT) at the nonrelativistic and scalar and SO-coupled relativistic levels, and also the *ab initio*-coupled cluster approach. The chemically active electron shells of the lanthanide atoms comprise the 5d and 6s (and 6p) valence atomic orbital (AO)s and also the filled inner 4f semivalence and outer 5p semicore shells. Four different frozen-core approximations for Lu were compared: the (1s^{2}–4d^{10}) [Pd] medium core, the [Pd+5s^{2}5p^{6} = Xe] and [Pd+4f^{14}] large cores, and the [Pd+4f^{14}+5s^{2}5p^{6}] very large core. The errors of LuX bonding are more serious on freezing the 5p^{6} shell than the 4f^{14} shell, more serious upon core-freezing than on the effective-core-potential approximation. The LnX distances correlate linearly with the AO radii of the ionic outer shells, Ln^{3+}-5p^{6} and X^{−}-*n*p^{6}, characteristic for dominantly ionic Ln^{3+}-X^{−} binding. The heavier halogen atoms also bind covalently with the Ln-5d shell. Scalar relativistic effects contract and destabilize the LuX bonds, spin orbit coupling hardly affects the geometries but the bond energies, owing to SO effects in the free atoms. The relativistic changes of bond energy BE, bond length *R*_{e}, bond force *k*, and bond stretching frequency *v*_{s} do not follow the simple rules of Badger and Gordy (*R*_{e}∼BE∼*k*∼*v*_{s}). The so-called degeneracy-driven covalence, meaning strong mixing of accidentally near-degenerate, nearly nonoverlapping AOs without BE contribution is critically discussed. © 2015 Wiley Periodicals, Inc.

The closed Lu 4f^{14} and 5s^{2}5p^{6} shells in LuX_{3} are not inert but influence the bonding, reproducible by wavefunction approaches. Accidental Ln-4f/F-2p near-degeneracy and AO-mixing is no evidence for covalence by noninteracting AOs. Fluorine causes overbinding with various DFs.

We describe the design of an object-oriented library of software components that are suitable for constructing simulations of systems of interacting particles. The emphasis of the discussion is on the general design of the components and how they interact, and less on details of the programming interface or its implementation. Example code is provided as an aid to understanding object-oriented programming structures and to demonstrate how the framework is applied. © 2015 Wiley Periodicals, Inc.

Molecular simulation methods find application to an extremely broad set of materials and phenomena, yet underlying this diversity is a unifying structure that can allow such variety to be realized using a relatively small set of software components. Ideas for the design of such a framework are discussed as is the implementation of it in a package we call *etomica*.

Enantioselectivity in the aza-Cope rearrangement of a guest molecule encapsulated in a cage-like supramolecular assembly [Ga_{4}L_{6}]^{12−} [L = 1,5-bis(2',3'-dihydroxybenzamido)naphthalene] is investigated using density functional theory and *ab initio* molecular orbital calculations. Reaction pathways leading to *R*- and *S*-enantiomers encapsulated in the [Ga_{4}L_{6}]^{12−} are explored. The reaction barriers and the stabilities of the prochiral structures differed in the [Ga_{4}L_{6}]^{12−}, resulting that the product with an *R* structure is favorably produced in the Δ-structure [Ga_{4}L_{6}]^{12−}. The large energy difference in the prochiral structures in the [Ga_{4}L_{6}]^{12−} was attributed to the deformation of the bulky substituent. The host–guest interaction energy raises the reaction barrier for the product with an *S* structure. The previous study suggested that the different stability of the prochiral substrates in the assembly was the origin of the enantioselectivity, and the suggestion is supported by our computational finding. In addition, our results show that the difference in the reaction barriers also importantly contributes to the enantioselectivity. © 2015 Wiley Periodicals, Inc.

The insights into the shape complementarity and host–guest interactions are important to design the supramolecular assemblies with high enantioselectivity. DFT investigation reveals that the reaction barriers and the stabilities of the prochiral structures of the aza-Cope rearrangement differed in the supramolecular assembly [Ga_{4}L_{6}]^{12−}, resulting that the substrate with an *R* structure is favorably produced in the Δ-structure [Ga_{4}L_{6}]^{12−}. The effects of the shape complementarity and host–guest interactions were analyzed.

The vibrational density of states (DoS), calculated from the Fourier transform of the velocity autocorrelation function, provides profound information regarding the structure and dynamic behavior of a system. However, it is often difficult to identify the exact vibrational mode associated with a specific frequency if the DoS is determined based on velocities in Cartesian coordinates. Here, the DoS is determined based on velocities in internal coordinates, calculated from Cartesian atomic velocities using a generalized Wilson's **B**-matrix. The DoS in internal coordinates allows for the correct detection of free dihedral rotations that may be mistaken as hindered rotation in Cartesian DoS. Furthermore, the pronounced enhancement of low frequency modes in Cartesian DoS for macromolecules should be attributed to the coupling of dihedral and angle motions. The internal DoS, thus deconvolutes the internal motions and provides fruitful insights to the dynamic behaviors of a system. © 2015 Wiley Periodicals, Inc.

The Wilson's **B**-matrix method is generalized to calculate internal coordinate density of state (DoS) of macromolecules. Compared with the Cartesian DoS where the normal modes are superposition of various internal modes, the internal DoS allows for a clear association of each vibrational modes with the dynamic behavior of a system, and thus provides a more natural way to describe molecular motion.

Essential Dynamics (ED) is a powerful tool for analyzing molecular dynamics (MD) simulations and it is widely adopted for conformational analysis of large molecular systems such as, for example, proteins and nucleic acids. In this study, we extend the use of ED to the study of clusters of arbitrary size constituted by weakly interacting particles, for example, atomic clusters and supramolecular systems. The key feature of the method we present is the identification of the relevant atomic-molecular clusters to be analyzed by ED for extracting the information of interest. The application of this computational approach allows a straightforward and unbiased conformational study of the local microstructures in liquids, as emerged from semiclassical MD simulations. The good performance of the method is demonstrated by calculating typical observables of liquid water, that is, NMR, NEXAFS O1s, and IR spectra, known to be rather sensitive both to the presence and to the conformational features of hydrogen-bonded clusters. © 2014 Wiley Periodicals, Inc.

A simple method, based on Essential Dynamics, is proposed for performing conformational analysis on clusters of arbitrary dimensions as provided by molecular dynamics (MD) simulations of liquids and solutions. The validity of the method is tested by modelling spectral observables of liquid water using a sequential procedure of configuration extraction from MD simulation and subsequent Quantum Chemical calculations.

Persistent homology is a relatively new tool often used for *qualitative* analysis of intrinsic topological features in images and data originated from scientific and engineering applications. In this article, we report novel *quantitative* predictions of the energy and stability of fullerene molecules, the very first attempt in using persistent homology in this context. The ground-state structures of a series of small fullerene molecules are first investigated with the standard Vietoris–Rips complex. We decipher all the barcodes, including both short-lived local bars and long-lived global bars arising from topological invariants, and associate them with fullerene structural details. Using accumulated bar lengths, we build quantitative models to correlate local and global Betti-2 bars, respectively with the heat of formation and total curvature energies of fullerenes. It is found that the heat of formation energy is related to the local hexagonal cavities of small fullerenes, while the total curvature energies of fullerene isomers are associated with their sphericities, which are measured by the lengths of their long-lived Betti-2 bars. Excellent correlation coefficients (>0.94) between persistent homology predictions and those of quantum or curvature analysis have been observed. A correlation matrix based filtration is introduced to further verify our findings. © 2014 Wiley Periodicals, Inc.

Geometric models often involve too much structural detail to be computationally efficient while topological models typically bear too little structural information to be quantitatively accurate. Persistent homology, a new branch of topology, bridges the gap between geometry and topology and offers a new strategy for handling big data. This work introduces persistent homology for qualitative analysis of fullerene topological fingerprints and quantitative prediction of fullerene stability.

The parameters obtained from a kinetic analysis of thermoanalytical data often exhibit a conversion-dependent behavior. A novel incremental isoconversional method able to deal with this phenomenon is proposed. The kinetic model is directly fitted to the experimental data using nonlinear orthogonal least squares procedure. The data are processed without transformations, so their error distribution is preserved. As the objective function is based on a maximum likelihood approach, reliable uncertainties of the parameters can be estimated. In contrast to other methods, the activation energy and the pre-exponential factor are treated as equally important kinetic parameters and are estimated simultaneously. Validity of the method is verified on simulated data, including a dataset with local nonlinearity in the temperature variation. A practical application on the nonisothermal cold crystallization of polyethylene terephthalate is presented. © 2014 Wiley Periodicals, Inc.

The parameters obtained from a kinetic analysis of thermoanalytical data often exhibit a conversion-dependent behavior. Modern isoconversional methods designed to deal with this problem are increasingly precise when applied to simulated data. Conversely, they do not take the errors of the measured data into account. The proposed incremental isoconversional method follows the error structure of the thermoanalytical measurements and the data are processed using the orthogonal distance regression without transformations.

The global minimum structures of AlB_{3}H_{2}* _{n}* (

The global minimum structures of AlB_{3}H_{2}n (*n* = 0–6) clusters are investigated and the chemical bonding patterns of the most stable isomers are analyzed by the adaptive natural density partitioning method.

A comparison between different conformations of a given protein, relating both structure and dynamics, can be performed in terms of combined principal component analysis (combined-PCA). To that end, a trajectory is obtained by concatenating molecular dynamics trajectories of the individual conformations under comparison. Then, the principal components are calculated by diagonalizing the correlation matrix of the concatenated trajectory. Since the introduction of this approach in 1995 it has had a large number of applications. However, the interpretation of the eigenvectors and eigenvalues so obtained is based on intuitive foundations, because analytical expressions relating the concatenated correlation matrix with those of the individual trajectories under consideration have not been provided yet. In this article, we present such expressions for the cases of two, three, and an arbitrary number of concatenated trajectories. The formulas are simple and show what is to be expected and what is not to be expected from a combined-PCA. Their correctness and usefulness is demonstrated by discussing some representative examples. The results can be summarized in a simple sentence: the correlation matrix of a concatenated trajectory is given by the average of the individual correlation matrices plus the correlation matrix of the individual averages. From this it follows that the combined-PCA of trajectories belonging to different free energy basins provides information that could also be obtained by alternative and more straightforward means. © 2014 Wiley Periodicals, Inc.

Combined principal component analysis (combined-PCA) is a technique usually employed to analyze structural and dynamical differences between alternative conformations of a given protein. However, analytical formulas showing what is to be expected and what is not to be expected from a combined-PCA have never been provided. Here, we present and discuss such formulas. We believe that they will be useful to enlighten the discussions of the results of combined-PCA.

We present a web toolkit STructure mapper and Online Coarse-graining Kit for setting up coarse-grained molecular simulations. The kit consists of two tools: structure mapping and Boltzmann inversion tools. The aim of the first tool is to define a molecular mapping from high, for example, all-atom, to low, that is, coarse-grained, resolution. Using a graphical user interface it generates input files, which are compatible with standard coarse-graining packages, for example, Versatile Object-oriented Toolkit for Coarse-graining Applications and DL_CGMAP. Our second tool generates effective potentials for coarse-grained simulations preserving the structural properties, for example, radial distribution functions, of the underlying higher resolution model. The required distribution functions can be provided by any simulation package. Simulations are performed on a local machine and only the distributions are uploaded to the server. The applicability of the toolkit is validated by mapping atomistic pentane and polyalanine molecules to a coarse-grained representation. Effective potentials are derived for systems of TIP3P (transferable intermolecular potential 3 point) water molecules and salt solution. The presented coarse-graining web toolkit is available at http://stock.cmm.ki.si. © 2014 Wiley Periodicals, Inc.

STOCK is a web-based toolkit for setting up coarse-grained molecular simulations. One can define a molecular mapping from high to low resolution with the aid of a molecular visualizer. Additionally, one may generate effective potentials for coarse-grained simulations preserving structural properties of the underlying higher resolution model. The tool is available at http://stock.cmm.ki.si

Datasets of molecular compounds often contain outliers, that is, compounds which are different from the rest of the dataset. Outliers, while often interesting may affect data interpretation, model generation, and decisions making, and therefore, should be removed from the dataset prior to modeling efforts. Here, we describe a new method for the iterative identification and removal of outliers based on a *k*-nearest neighbors optimization algorithm. We demonstrate for three different datasets that the removal of outliers using the new algorithm provides filtered datasets which are better than those provided by four alternative outlier removal procedures as well as by random compound removal in two important aspects: (1) they better maintain the diversity of the parent datasets; (2) they give rise to quantitative structure activity relationship (QSAR) models with much better prediction statistics. The new algorithm is, therefore, suitable for the pretreatment of datasets prior to QSAR modeling. © 2014 Wiley Periodicals, Inc.

A new iterative method for the identification and removal of outliers from quantitative structure activity relationship (QSAR) datasets is described. This method is based on a *k*NN optimization algorithm, and named *k*NN optimization-based outlier removal. The method is able to maintain the internal diversity of the parent dataset and at the same time produce QSAR models with better prediction statistics than other outlier removal methods.

We comprehensively illustrate a general process of fitting all-atom molecular mechanics force field (FF) parameters based on quantum mechanical calculations and experimental thermodynamic data. For common organic molecules with free dihedral rotations, this FF format is comprised of the usual bond stretching, angle bending, proper and improper dihedral rotation, and 1–4 scaling pair interactions. An extra format of 1–*n* scaling pair interaction is introduced when a specific intramolecular rotation is strongly hindered. We detail how the preferred order of fitting all intramolecular FF parameters can be determined by systematically generating characteristic configurations. The intermolecular Van der Waals parameters are initially taken from the literature data but adjusted to obtain a better agreement between the molecular dynamics (MD) simulation results and the experimental observations if necessary. By randomly choosing the molecular configurations from MD simulation and comparing their energies computed from FF parameters and quantum mechanics, the FF parameters can be verified self-consistently. Using an example of a platform chemical 3-hydroxypropionic acid, we detail the comparison between the new fitting parameters and the existing FF parameters. In particular, the introduced systematic approach has been applied to obtain the dihedral angle potential and 1–*n* scaling pair interaction parameters for 48 organic molecules with different functionality. We suggest that this procedure might be used to obtain better dihedral and 1–*n* interaction potentials when they are not available in the current widely used FF. © 2014 Wiley Periodicals, Inc.

The energy correlation map between calculations from molecular mechanics force fields and quantum mechanical calculations illustrating the quality of the developed force field to describe the transition energies for condensed matter systems of ethane (right) and 3-hydroxypropionic acid (left). Especially for the 3-hydroxypropionic acid molecule, the parameters for the dihedral angle and 1−*n* interaction potentials in the new force field (MM) significantly help to improve the results in comparison to QM studies.

Hydrophobic Interactions (HIs) are important in many phenomena of molecular recognition in chemistry and biology. Still, the relevance of HIs is sometimes difficult to evaluate particularly in large systems and intramolecular interactions. We put forward a method to estimate the magnitude and the different contributions of a given HI of the C···C, HC···H, and H···H type through (i) the analysis of the electron density in the intermolecular region for eleven relative orientations of the methane dimer and (ii) the subsequent decomposition of the corresponding interaction energy in physically significant contributions using Symmetry Adapted Perturbation Theory (SAPT). Strong correlations were found between the topological properties of
calculated at intermolecular bond critical points and
plus its different contributions with the C···C distance of the considered orientations of (CH_{4})_{2}. These correlations were used to construct Mollier-like diagrams of
and its components as a function of the separation between two carbons and the orientation of the groups bonded to these atoms. The ethane dimer and *tert*-butylcyclohexane are used as representative examples of this new approach. Overall, we anticipate that this new method might prove useful in the study of both intramolecular and intermolecular HIs particularly of those within large systems wherein SAPT or electronic structure calculations are computationally expensive or even prohibitive. © 2014 Wiley Periodicals, Inc.

Eleven relative orientations of (CH_{4})_{2} were investigated through the topology of
and Symmetry Adapted Perturbation Theory (SAPT). The relations found between the components of SAPT and the properties of
are exploited to construct Mollier-like diagrams to evaluate the importance of hydrophobic interactions (HIs) in representative examples. These diagrams might prove useful in analyzing HIs, especially when ab-initio or SAPT calculations are unfeasible or prohibitively expensive.

Designing and characterizing the compounds with exotic structures and bonding that seemingly contrast the traditional chemical rules are a never-ending goal. Although the silicon chemistry is dominated by the tetrahedral picture, many examples with the planar tetracoordinate-Si skeletons have been discovered, among which simple species usually contain the 17/18 valence electrons. In this work, we report hitherto the most extensive structural search for the pentaatomic ptSi with 14 valence electrons, that is,
(*n* + *m* = 4; *q* = 0, ±1, −2; X, Y = main group elements from H to Br). For 129 studied systems, 50 systems have the ptSi structure as the local minimum. Promisingly, nine systems, that is,
, HSiY_{3} (Y = Al/Ga), Ca_{3}SiAl^{−}, Mg_{4}Si^{2−}, C_{2}LiSi, Si_{3}Y_{2} (Y = Li/Na/K), each have the global minimum ptSi. The former six systems represent the first prediction. Interestingly, in HSiY_{3} (Y = Al/Ga), the H-atom is only bonded to the ptSi-center via a localized 2c–2e σ bond. This sharply contradicts the known pentaatomic planar-centered systems, in which the ligands are actively involved in the ligand–ligand bonding besides being bonded to the planar center. Therefore, we proposed here that to generalize the 14e-ptSi, two strategies can be applied as (1) introducing the alkaline/alkaline-earth elements and (2) breaking the peripheral bonding. In light of the very limited global ptSi examples, the presently designed six systems with 14e are expected to enrich the exotic ptSi chemistry and welcome future laboratory confirmation. © 2014 Wiley Periodicals, Inc.

The 14 electrons of planar tetracoordinate silicon were systematically searched for the first time, finding nine global minimum ptSi, that is, Li_{3}SiAs^{2−}, HSiY_{3} (Y = Al/Ga), Ca_{3}SiAl^{−}, Mg_{4}Si^{2−}, C_{2}LiSi, Si_{3}Y_{2} (Y = Li/Na/K). The former six systems represent the first prediction. In light of the very limited global ptSi examples, the presently designed six systems with 14e are expected to enrich the exotic ptSi chemistry and welcome future laboratory confirmation.

On page 273 (DOI: 10.1002/jcc.23800), Dmitry Zuev, Eugene Vecharynski, Chao Yang, Natalie Orms, and Anna I. Krylov report on new iterative diagonalization algorithms targeting interior eigenstates of large matrices, which enable calculations of highly excited states within equation-of-motion coupled-cluster framework.

A graphical user interface (VMS-Draw) for a virtualmultifrequency spectrometer provides user-friendly access to the latest developments of computational spectroscopy. Also appropriate for nonspecialists, Daniele Licari, Alberto Baiardi, Malgorzata Biczysko, Franco Egidi, Camille Latouche, and Vincenzo Barone report on page 321 (DOI: 10.1002/jcc.23785) that VMS-Draw produces various graphical representations, offering invaluable aid in organizing and clearly presenting the information produced by computations. Special attention is paid to ease of use, generality, and robustness for a panel of spectroscopic techniques and quantum mechanical approaches. Among other integrated features, one may quote the visualization and analysis of vibrationally resolved electronic or anharmonic vibrational spectra, including convolution of stick spectra, to obtain realistic line-shapes.

Todor Dudev,Mike Devereux, Markus Meuwly, Carmay Lim, Jean-Philip Piquemal and Nohad Gresh present on page 285 (DOI: 10.1002/jcc.23801) a new parametrization of thewell-established, polarizable SIBFA force field for the series of Li^{+}—Cs^{+} alkali cations, which are of outstanding importance in a diversity of biochemical and bioinorganic processes. With direct application to the study of cation selectivity, illustrated here by Na^{+} at the mouth of a sodium ion channel, the delicate balance between different competing structures waswell accounted for using polarizablemolecular mechanics for the series of test complexes included in the study.

New algorithms for iterative diagonalization procedures that solve for a small set of eigen-states of a large matrix are described. The performance of the algorithms is illustrated by calculations of low and high-lying ionized and electronically excited states using equation-of-motion coupled-cluster methods with single and double substitutions (EOM-IP-CCSD and EOM-EE-CCSD). We present two algorithms suitable for calculating excited states that are close to a specified energy shift (interior eigenvalues). One solver is based on the Davidson algorithm, a diagonalization procedure commonly used in quantum-chemical calculations. The second is a recently developed solver, called the “Generalized Preconditioned Locally Harmonic Residual (GPLHR) method.” We also present a modification of the Davidson procedure that allows one to solve for a specific transition. The details of the algorithms, their computational scaling, and memory requirements are described. The new algorithms are implemented within the EOM-CC suite of methods in the Q-Chem electronic structure program. © 2014 Wiley Periodicals, Inc.

Finding a few eigenpairs of large matrices is a common task in science and engineering. In the present work, new algorithms are introduced for iterative diagonalization that solve for a small set of eigenstates of a large matrix. A modified version of Davidson's algorithm enabling a user to solve for interior eigenpairs at low computational cost is presented. A new solver is also introduced, and its performance is compared against the canonical Davidson procedure.

The alkali metal cations in the series Li^{+}Cs^{+} act as major partners in a diversity of biological processes and in bioinorganic chemistry. In this article, we present the results of their calibration in the context of the SIBFA polarizable molecular mechanics/dynamics procedure. It relies on quantum-chemistry (QC) energy-decomposition analyses of their monoligated complexes with representative O, N, S, and Se ligands, performed with the aug-cc-pVTZ(-f) basis set at the Hartree–Fock level. Close agreement with QC is obtained for each individual contribution, even though the calibration involves only a limited set of cation-specific parameters. This agreement is preserved in tests on polyligated complexes with four and six O ligands, water and formamide, indicating the transferability of the procedure. Preliminary extensions to density functional theory calculations are reported.

In the context of the SIBFA polarizable molecular mechanics procedure, the alkali cations in the series Li^{+}Cs^{+} are calibrated and validated. This is done upon referring to *ab initio* quantum-chemical calculations at the aug-cc-pVTZ(-f) level, with representative O-, N-, S-, and Se-based ligands. The validations are done on several polycoordinated complexes of these cations, and a close reproduction of the quantum chemical results can be obtained.

We report the implementation of the local response dispersion (LRD) method in an electronic structure program package aimed at periodic systems and an assessment combined with the Perdew–Burke–Ernzerhof (PBE) functional and its revised version (revPBE). The real-space numerical integration was implemented and performed exploiting the electron distribution given by the plane-wave basis set. The dispersion-corrected density functionals revPBE+LRD was found to be suitable for reproducing energetics, structures, and electron distributions in simple substances, molecular crystals, and physical adsorptions. © 2014 Wiley Periodicals, Inc.

The local response dispersion (LRD) method, which has been developed as a dispersion correction method for isolated molecules, is implemented in the package based on periodic boundary condition and plane-wave basis set. After atomic polarizabilities are calculated using the real-space grid, the dispersion energy is obtained as the sum of atomic pair contributions. The availability of LRD with PBE and revPBE functionals is assessed for simple substances, molecular crystals, and physical adsorption.

The article introduces a robust algorithm for the computation of minimum energy paths transiting along regions of near-to or degeneracy of adiabatic states. The method facilitates studies of excited state reactivity involving weakly avoided crossings and conical intersections. Based on the analysis of the change in the multiconfigurational wave function the algorithm takes the decision whether the optimization should continue following the same electronic state or switch to a different state. This algorithm helps to overcome convergence difficulties near degeneracies. The implementation in the MOLCAS quantum chemistry package is discussed. To demonstrate the utility of the proposed procedure four examples of application are provided: thymine, asulam, 1,2-dioxetane, and a three-double-bond model of the 11-*cis*-retinal protonated Schiff base. © 2015 Wiley Periodicals, Inc.

A new computational scheme that combines a simulation technique to find a minimum energy path and an algorithm to switch between different electronic states is presented. It is applied to study the photochemical reaction path of four different molecules.

This article presents the setup and implementation of a graphical user interface (VMS-Draw) for a virtual multifrequency spectrometer. Special attention is paid to ease of use, generality and robustness for a panel of spectroscopic techniques and quantum mechanical approaches. Depending on the kind of data to be analyzed, VMS-Draw produces different types of graphical representations, including two-dimensional or three-dimesional (3D) plots, bar charts, or heat maps. Among other integrated features, one may quote the convolution of stick spectra to obtain realistic line-shapes. It is also possible to analyze and visualize, together with the structure, the molecular orbitals and/or the vibrational motions of molecular systems thanks to 3D interactive tools. On these grounds, VMS-Draw could represent a useful additional tool for spectroscopic studies integrating measurements and computer simulations. © 2014 Wiley Periodicals, Inc.

This article presents the setup and implementation of a new graphical user interface (VMS-Draw) for a multifrequency spectrometer. Among other integrated features, one may quote the convolution of stick spectra to obtain realistic line-shapes. It is also possible to analyze and visualize, together with the structure, the molecular orbitals and/or the vibrational motions of molecular systems thanks to 3D interactive tools.

We present the generic, object-oriented C++ implementation of the completeness-optimization approach (Manninen and Vaara, J. Comput. Chem. 2006, 27, 434) in the freely available ERKALE program, and recommend the addition of basis set stability scans to the completeness-optimization procedure. The design of the algorithms is independent of the studied property, the used level of theory, as well as of the role of the optimized basis set: the procedure can be used to form auxiliary basis sets in a similar fashion. This implementation can easily be interfaced with various computer programs for the actual calculation of molecular properties for the optimization, and the calculations can be trivially parallelized. Routines for general and segmented contraction of the generated basis sets are also included. The algorithms are demonstrated for two properties of the argon atom—the total energy and the nuclear magnetic shielding constant—and they will be used in upcoming work for generation of cost-efficient basis sets for various properties. © 2014 Wiley Periodicals, Inc.

The completeness-optimization procedure is based on a sequence of consecutive additions of functions into the basis set, illustrated here for augmentation with tight and diffuse functions, until the studied property attains convergence to the complete basis set limit. Once the limit has been achieved, the procedure is run in reverse to form computationally efficient basis sets for production-level calculations.

Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics-based alchemical free energy calculations are unique in their accuracy and solid theoretical basis. The challenge in using these methods lies in the need to generate hybrid structures and topologies representing two physical states of a system. A custom made hybrid topology may prove useful for a particular mutation of interest, however, a high throughput mutation analysis calls for a more general approach. In this work, we present an automated procedure to generate hybrid structures and topologies for the amino acid mutations in all commonly used force fields. The described software is compatible with the Gromacs simulation package. The mutation libraries are readily supported for five force fields, namely Amber99SB, Amber99SB*-ILDN, OPLS-AA/L, Charmm22*, and Charmm36. © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Molecular dynamics-based alchemical free energy calculations present a powerful method to evaluate protein thermostability and changes in the interaction affinities upon an amino acid mutation. The approach requires a description of the mutatable amino acids as a two state system connected via an alchemical pathway. In the current work, we present a framework and its implementation to generate hybrid amino acid structures and topologies for a number of commonly used biomolecular force fields.