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.

The transport of ions and solutes by biological pores is central for cellular processes and has a variety of applications in modern biotechnology. The time scale involved in the polymer transport across a nanopore is beyond the accessibility of conventional MD simulations. Moreover, experimental studies lack sufficient resolution to provide details on the molecular underpinning of the transport mechanisms. BROMOC, the code presented herein, performs Brownian dynamics simulations, both serial and parallel, up to several milliseconds long. BROMOC can be used to model large biological systems. IMC-MACRO software allows for the development of effective potentials for solute–ion interactions based on radial distribution function from all-atom MD. BROMOC Suite also provides a versatile set of tools to do a wide variety of preprocessing and postsimulation analysis. We illustrate a potential application with ion and ssDNA transport in MspA nanopore. © 2014 Wiley Periodicals, Inc.

The transport of DNA and ions by biological pores is central for cellular processes and has a variety of applications in modern biotechnology. BROMOC Suite is a software package designed to perform Brownian dynamics simulations up to several milliseconds long of large biological systems (BROMOC), to develop effective potentials for solute-ion interactions based on RDF from all-atom Molecular Dynamics (IMC-MACRO), and to do a wide variety of pre-processing and post-simulation analysis (BROMOC Tools).

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.

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 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.

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.

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.

Proteins are an important class of biomolecules with applications spanning across biotechnology and medicine. In many cases, native proteins must be redesigned to improve various performance metrics by changing their amino acid sequences. Algorithms can help sharpen protein library design by focusing the library on sequences that optimize computationally accessible proxies. The Iterative Protein Redesign and Optimization (IPRO) suite of programs offers an integrated environment for (1) altering protein binding affinity and specificity, (2) grafting a binding pocket into an existing protein scaffold, (3) predicting an antibody's tertiary structure based on its sequence, (4) enhancing enzymatic activity, and (5) assessing the structure and binding energetics for a specific mutant. This manuscript provides an overview of the methods involved in IPRO, input language terminology, algorithmic details, software implementation specifics and application highlights. IPRO can be downloaded at http://maranas.che.psu.edu. © 2014 Wiley Periodicals, Inc.

The Iterative Protein Redesign and Optimization suite of programs integrates various methods for protein engineering. All of these methods incorporate the same fundamental idea that improving the affinity for a small molecule can be achieved by repeatedly perturbing the protein's backbone, finding the optimal set of amino acids based on this new backbone conformation, making minor adjustments to the protein's structure and small molecule's orientation, and deciding to keep the results or not.

The capabilities of an adaptive Cartesian grid (ACG)-based Poisson–Boltzmann (PB) solver (CPB) are demonstrated. CPB solves various PB equations with an ACG, built from a hierarchical octree decomposition of the computational domain. This procedure decreases the number of points required, thereby reducing computational demands. Inside the molecule, CPB solves for the reaction-field component (*ϕ*_{rf}) of the electrostatic potential (*ϕ*), eliminating the charge-induced singularities in *ϕ*. CPB can also use a least-squares reconstruction method to improve estimates of *ϕ* at the molecular surface. All surfaces, which include solvent excluded, Gaussians, and others, are created analytically, eliminating errors associated with triangulated surfaces. These features allow CPB to produce detailed surface maps of *ϕ* and compute polar solvation and binding free energies for large biomolecular assemblies, such as ribosomes and viruses, with reduced computational demands compared to other Poisson–Boltzmann equation solvers. The reader is referred to http://www.continuum-dynamics.com/solution-mm.html for how to obtain the CPB software. © 2014 Wiley Periodicals, Inc.

Electrostatic potential maps and polar solvation (Δ*G*_{el}) and binding (ΔΔ*G*_{el}) energies computed with the Poisson–Boltzmann equation (PBE) are widely used in biophysical applications. By using an adaptive Cartesian grid and least-squares reconstruction schemes, the PBE solver CPB can produce high resolution surface electrostatic potential maps and predict Δ*G*_{el} and ΔΔ*G*_{el} for large biomolecular assemblies, such as ribosomes and viruses, with lower computational demands than other PBE solvers.

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.

The Quantum-to-molecular mechanics method (Q2MM) for converting quantum mechanical transition states (TSs) to molecular mechanical minima has been modified to allow a fit to the “natural” reaction mode eigenvalue. The resulting force field gives an improved representation of the energy curvature at the TS, but can potentially give false responses to steric interactions. Ways to address this problem while staying close to the “natural” TS force field are discussed. © 2014 Wiley Periodicals, Inc.

The Quantum-to-molecular mechanics method for parameterization of force fields has been augmented by a projection along normal modes, allowing a close fit to natural force constants while retaining a positive curvature at the TS.

The symmetry of molecules and transition states of elementary reactions is an essential property with important implications for computational chemistry. The automated identification of symmetry by computers is a very useful tool for many applications, but often relies on the availability of three-dimensional coordinates of the atoms in the molecule and hence becomes less useful when these coordinates are *a priori* unavailable. This article presents a new algorithm that identifies symmetry of molecules and transition states based on an augmented graph representation of the corresponding structures, in which both topology and the presence of stereocenters are accounted for. The automorphism group order of the graph associated with the molecule or transition state is used as a starting point. A novel concept of label-stereoisomers, that is, stereoisomers that arise after labeling homomorph substituents in the original molecule so that they become distinguishable, is introduced and used to obtain the symmetry number. The algorithm is characterized by its generic nature and avoids the use of heuristic rules that would limit the applicability. The calculated symmetry numbers are in agreement with expected values for a large and diverse set of structures, ranging from asymmetric, small molecules such as fluorochlorobromomethane to highly symmetric structures found in drug discovery assays. The new algorithm opens up new possibilities for the fast screening of the degree of symmetry of large sets of molecules. © 2014 Wiley Periodicals, Inc.

The fast and accurate automated calculation of the rotational symmetry number of molecule opens up an array of applications in computational chemistry. This work discusses a novel algorithm for the determination of symmetry numbers based on an augmented graph representation of the chemical structure. The general applicability for a diverse range of molecules and transition states is illustrated. The application of the algorithm on a database of 50,000 molecules is presented as a test case.

The excited states of the phenylene ethynylene dendrimer are investigated comprehensively by various electronic-structure methods. Several computational methods, including SCS-ADC(2), TDHF, TDDFT with different functionals (B3LYP, BH&HLYP, CAM-B3LYP), and DFT/MRCI, are applied in systematic calculations. The theoretical approach based on the one-electron transition density matrix is used to understand the electronic characters of excited states, particularly the contributions of local excitations and charge-transfer excitations within all interacting conjugated branches. Furthermore, the potential energy curves of low-lying electronic states as the functions of ethynylene bonds are constructed at different theoretical levels. This work provides us theoretical insights on the intramolecular excited-state energy transfer mechanism of the dendrimers at the state-of-the-art electronic-structure theories. © 2014 Wiley Periodicals, Inc.

The systematical calculations with different levels of electronic-structure methods are conducted to understand the optoelectronic properties of conjugated dendrimers. The electronic characters of excited states, namely the contributions of intraunit local excitations and interunit charge-transfer excitations within all interacting conjugated branches, are analyzed by the one-electron transition density matrix. This work provides theoretical insights of photoinduced energy transfer in solar energy conversions for novel tree-like photovoltaic materials.

A procedure to automatically find the transition states (TSs) of a molecular system (MS) is proposed. It has two components: high-energy chemical dynamics simulations (CDS), and an algorithm that analyzes the geometries along the trajectories to find reactive pathways. Two levels of electronic structure calculations are involved: a low level (LL) is used to integrate the trajectories and also to optimize the TSs, and a higher level (HL) is used to reoptimize the structures. The method has been tested in three MSs: formaldehyde, formic acid (FA), and vinyl cyanide (VC), using MOPAC2012 and Gaussian09 to run the LL and HL calculations, respectively. Both the efficacy and efficiency of the method are very good, with around 15 TS structures optimized every 10 trajectories, which gives a total of 7, 12, and 83 TSs for formaldehyde, FA, and VC, respectively. The use of CDS makes it a powerful tool to unveil possible nonstatistical behavior of the system under study. © 2014 Wiley Periodicals, Inc.

An automated method to optimize the transition states of a molecular system is proposed. Based on running high-energy chemical dynamics simulations, it sampled different areas of the potential energy surface. Then, an algorithm was used to select suitable candidate structures to be optimized as transition states. As dynamics simulations were involved in the procedure, additional information about the system was obtained, as the possibility of deviations from statistical behavior.

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.

Several computational methods, both semiempirical and *ab initio,* were used to study the influence of the amount of dopant on crystal cell dimensions of CeF_{3} doped with Tb^{3+} ions (CeF_{3}:Tb^{3+}). AM1, RM1, PM3, PM6, and PM7 semiempirical parameterization models were used, while the Sparkle model was used to represent the lanthanide cations in all cases. *Ab initio* calculations were performed by means of GGA+U/PBE projector augmented wave density functional theory. The computational results agree well with the experimental data. According to both computation and experiment, the crystal cell parameters undergo a linear decrease with increasing amount of the dopant. The computations performed using Sparkle/PM3 and DFT methods resulted in the best agreement with the experiment with the average deviation of about 1% in both cases. Typical Sparkle/PM3 computation on a 2×2×2 supercell of CeF3:Tb3+ lasted about two orders of magnitude shorter than the DFT computation concerning a unit cell of this material. © 2014 Wiley Periodicals, Inc.

The AM1, RM1, PM3, PM6, and PM7 semiempirical computational methods with Sparkle model for Ln(III) and GGA/PBE *ab initio* DFT method were used to model the influence of the amount of dopant on crystal cell dimensions of CeF_{3} doped with Tb^{3+} ions, a known luminescent material. The cell dimensions of the material calculated using Sparkle/PM3 and the DFT methods were in the best agreement (about 1% error) with our experimental data on CeF_{3}:Tb^{3+} obtained via co-precipitation or hydrothermal methods.

The CX bond in halobenzenes (XCl, Br) exhibits a dual character, being electron-deficient along the CX direction, and electron-rich on its flanks. We sought to amplify both features by resorting to electron-withdrawing and electron-donating substituents, respectively. This was done by quantum chemistry (QC) computations in the recognition sites of three protein targets: farnesyl transferase, coagulation factor Xa, and the HIV-1 integrase. In this context, some substituents, notably fluorine, CF_{3}, and NHCH_{3}, afforded significant overall gains in the binding energies as compared to the parent halobenzene, in the 2–5 kcal/mol range. In fact, we found that some di- and up to tetra-substitutions enabled even larger gains than those they contribute separately owing to many-body effects. Moreover, desolvation was also found to be a key contributor to the energy balances. As a consequence, some particular substituents, contributing to reduce the halobenzene dipole moment, accordingly reduced solvation: this factor acted in synergy with their enhancement of the intermolecular interaction energies along and around the CX bond. We could thus leverage the “Janus-like” properties of such a bond and the fact that it can be tuned and possibly amplified by well-chosen substituents. We propose a simple yet rigorous computational strategy resorting to QC to prescreen novel substituted halobenzenes. The QC results on the recognition sites then set benchmarks to validate polarizable molecular mechanics/dynamics approaches used to handle the entirety of the inhibitor-protein complex. © 2014 Wiley Periodicals, Inc.

The CX bond in halobenzenes (XCl, Br) exhibits a dual character, electron-deficient along the CX direction, and electron-rich on its flanks. Both features were amplified upon resorting to electron-withdrawing and -donating substituents respectively. This was done by quantum chemistry computations in the recognition sites of three protein targets. A simple yet rigorous computational strategy is suggested to prescreen novel substituted halobenzenes in the context of drug design.

The water/aromatic parallel alignment interactions are interactions where the water molecule or one of its OH bonds is parallel to the aromatic ring plane. The calculated energies of the interactions are significant, up to Δ*E*_{CCSD(T)(limit)} = −2.45 kcal mol^{−1} at large horizontal displacement, out of benzene ring and CH bond region. These interactions are stronger than CH···O water/benzene interactions, but weaker than OH···π interactions. To investigate the nature of water/aromatic parallel alignment interactions, energy decomposition methods, symmetry-adapted perturbation theory, and extended transition state-natural orbitals for chemical valence (NOCV), were used. The calculations have shown that, for the complexes at large horizontal displacements, major contribution to interaction energy comes from electrostatic interactions between monomers, and for the complexes at small horizontal displacements, dispersion interactions are dominant binding force. The NOCV-based analysis has shown that in structures with strong interaction energies charge transfer of the type π σ*(OH) between the monomers also exists. © 2014 Wiley Periodicals, Inc.

The nature of interactions in parallel water/benzene complexes is investigated using *ab initio* calculations and energy decomposition methods. The calculated energies of the interactions are significant at large horizontal displacement. These interactions are stronger than CH…O water/benzene interactions, but weaker than OH…π interactions. Both energy decomposition methods, SAPT and ETS-NOCV, agree that electrostatic is the most important force, responsible for bonding in water/benzene parallel complexes at large horizontal displacement.

Graphical processing units (GPUs) are emerging in computational chemistry to include Hartree−Fock (HF) methods and electron-correlation theories. However, *ab initio* calculations of large molecules face technical difficulties such as slow memory access between central processing unit and GPU and other shortfalls of GPU memory. The divide-and-conquer (DC) method, which is a linear-scaling scheme that divides a total system into several fragments, could avoid these bottlenecks by separately solving local equations in individual fragments. In addition, the resolution-of-the-identity (RI) approximation enables an effective reduction in computational cost with respect to the GPU memory. The present study implemented the DC-RI-HF code on GPUs using math libraries, which guarantee compatibility with future development of the GPU architecture. Numerical applications confirmed that the present code using GPUs significantly accelerated the HF calculations while maintaining accuracy. © 2014 Wiley Periodicals, Inc.

The graphical processing units (GPU) implementations were performed for accelerating the Hartree–Fock (HF) calculations by combining the linear-scaling divide-and-conquer (DC) method with the effective resolution-of-the-identity (RI) technique. The speedups of DC-RI-HF on GPU compared with standard HF increased with increasing molecular size because of the sparse density matrix and local diagonalization by the DC method.

Common trends in communication through molecular bridges are ubiquitous in chemistry, such as the frequently observed exponential decay of conductance/electron transport and of exchange spin coupling with increasing bridge length, or the increased communication through a bridge upon closing a diarylethene photoswitch. For antiferromagnetically coupled diradicals in which two equivalent spin centers are connected by a closed-shell bridge, the molecular orbitals (MOs) whose energy splitting dominates the coupling strength are similar in shape to the MOs of the dithiolated bridges, which in turn can be used to rationalize conductance. Therefore, it appears reasonable to expect the observed common property trends to result from common orbital trends. We illustrate based on a set of model compounds that this assumption is not true, and that common property trends result from either different pairs of orbitals being involved, or from orbital energies not being the dominant contribution to property trends. For substituent effects, an effective modification of the π system can make a comparison difficult. © 2014 Wiley Periodicals, Inc.

Communication through molecular bridges plays a crucial role in electron transfer, charge or spin delocalization in mixed-valence compounds, electron transport, and electron spin coupling through superexchange. For the latter two, common property trends are found to not result from common bridge molecular orbital energy trends, so transferring knowledge from electron transport to spin coupling based on bridge orbitals is not straightforward.

Fullerenes and their structure and stability have been a major topic of discussion and research since their discovery nearly 30 years ago. The isolated pentagon rule (IPR) has long served as a guideline for predicting the most stable fullerene cages. More recently, endohedral metallofullerenes have been discovered that violate the IPR. This article presents a systematic, temperature dependent, statistical thermodynamic study of the 24 possible IPR isomers of C_{84} as well as two of the experimentally known non-IPR isomers (51365 and 51383), at several different charges (0, −2, −4, and −6). From the results of this study, we conclude that the Hückel rule is a valid simpler explanation for the stability of fused pentagons in endohedral metallofullerenes. © 2014 Wiley Periodicals, Inc.

A systematic, temperature dependent, statistical thermodynamic study is presented of the 24 possible isolated pentagon rule fullerene isomers of C_{84} as well as two of the experimentally known non-IPR isomers (51365 and 51383), at several different charges (0, −2, −4, and −6). Based on the results, the Hückel rule is a valid explanation for the stability of fused pentagons in endohedral metallofullerenes.

Within the framework of the Förster theory, the electronic excitation energy transfer pathways in the cyanobacteria allophycocyanin (APC) trimer and hexamer were studied. The associated physical quantities (i.e., excitation energy, oscillator strength, and transition dipole moments) of the phycocyanobilins (PCBs) located in APC were calculated at time-dependent density functional theory (TDDFT) level of theory. To estimate the influence of protein environment on the preceding calculated physical quantities, the long-range interactions were approximately considered with the polarizable continuum model at the TDDFT level of theory, and the short-range interaction caused by surrounding aspartate residue of PCBs were taken into account as well. The shortest energy transfer time calculated in the framework of the Förster model at TDDFT/B3LYP/6–31+G* level of theory are about 0.10 ps in the APC trimer and about 170 ps in the APC monomer, which are in qualitative agreement with the experimental finding that a very fast lifetime of 0.43–0.44 ps in APC trimers, whereas its monomers lacked any corresponding lifetime. These results suggest that the lifetime of 0.43–0.44 ps in the APC trimers determined by Sharkov et al. was most likely attributed to the energy transfer of *α*^{1}-84 *β*^{3}-84 (0.23 ps), *β*^{1}-84 *α*^{2}-84 (0.11 ps) or *β*^{2}-84 *α*^{3}-84 (0.10 ps). So far, no experimental or theoretical energy transfer rates between two APC trimmers were reported, our calculations predict that the predominate energy transfer pathway between APC trimers is likely to occur from *α*^{3}-84 in one trimer to *α*^{5}-84 in an adjacent trimer with a rate of 32.51 ps. © 2014 Wiley Periodicals, Inc.

The electronic energy transfer is a fundamental key in the development of synthetic light-harvesting devices. Insight into the EET pathways in APC trimer and hexamer was gained by the first principle calculations within the framework of Förster theory.

Aqueous p*K*_{A} values for hexa-aqua complexes of first and second row transition metals are computed using a combination of quantum chemical and electrostatic methods. On page 69 (DOI: 10.1002/jcc.23764), Gegham Galstyan and Ernst-Walter Knapp report the computed p*K*_{A} values show very good agreement with measured p*K*_{A} values with a root mean square deviation of 1 pH unit. Compared to previous approaches, the precision of the method is systematically improved.

On page 79 (DOI: 10.1002/jcc.23775), Robin M. Betz and Ross C. Walker report on Paramfit, a new program that generates force field parameters for molecular dynamics simulation by minimizing the difference between *ab-initio* quantum and classical energies of a set of input molecular conformations. The program incorporates a novel minimization algorithm capable of reliably locating global minima, shown by testing on various surfaces like the three-dimensional Rastrigin function illustrated here, which features numerous attractive local minima. Several molecular conformations of a small peptide used for demonstrating the program's efficacy on biological systems are also shown at the border. Structures like these are input into Paramfit, along with associated quantum energies, and are used to generate parameters of interest.

Encapsulating rare-gas atoms into fullerenes smaller than C_{60} quickly becomes repulsive and follows an exponential law with decreasing number of carbon atoms. The reason comes from a rather rigid cage structure that determines the space available inside the fullerene. On page 88 (DOI: 10.1002/jcc.23787), Rebecca Sure, Ralf Tonner, and Peter Schwerdtfeger provide detailed insight into rare-gas fullerene interactions ranging from C_{20} to C_{60} and from He to Ar using Grimme's dispersion corrected density functional theory. The maximum inscribing inner sphere inside a fullerene cage gives a good qualitative picture for the space available.

Aqueous p*K*_{A} values for 15 hexa-aqua transition metal complexes were computed using a combination of quantum chemical and electrostatic methods. Two different structure models were considered optimizing the isolated complexes in vacuum or in presence of explicit solvent using a QM/MM approach. They yield very good agreement with experimentally measured p*K*_{A} values with an overall root mean square deviation of about 1 pH unit, excluding a single but different outlier for each of the two structure models. These outliers are hexa-aqua Cr(III) for the vacuum and hexa-aqua Mn(III) for the QM/MM structure model. Reasons leading to the deviations of the outlier complexes are partially explained. Compared to previous approaches from the same lab the precision of the method was systematically improved as discussed in this study. The refined methods to obtain the appropriate geometries of the complexes, developed in this work, may allow also the computation of accurate p*K*_{A} values for multicore transition metal complexes in different oxidation states. © 2014 Wiley Periodicals, Inc.

Aqueous p*K*_{A} values for hexa-aqua complexes of first and second row transition metals were computed using a combination of quantum chemical and electrostatic methods. Computed p*K*_{A} values show very good agreement with measured p*K*_{A} values with a root mean square deviation of 1 pH unit. Compared to previous approaches from the same lab, the precision of the method was systematically improved.

The generation of bond, angle, and torsion parameters for classical molecular dynamics force fields typically requires fitting parameters such that classical properties such as energies and gradients match precalculated quantum data for structures that scan the value of interest. We present a program, Paramfit, distributed as part of the AmberTools software package that automates and extends this fitting process, allowing for simplified parameter generation for applications ranging from single molecules to entire force fields. Paramfit implements a novel combination of a genetic and simplex algorithm to find the optimal set of parameters that replicate either quantum energy or force data. The program allows for the derivation of multiple parameters simultaneously using significantly fewer quantum calculations than previous methods, and can also fit parameters across multiple molecules with applications to force field development. Paramfit has been applied successfully to systems with a sparse number of structures, and has already proven crucial in the development of the Assisted Model Building with Energy Refinement Lipid14 force field. © 2014 Wiley Periodicals, Inc.

Classical molecular dynamics parameters are obtained by fitting so that the energy of a set of structures calculated with the parameters matches a set of input energies calculated at a quantum level of theory. The Paramfit program automates this fitting process using a novel hybrid of genetic and simplex algorithms to fit multiple parameters simultaneously to any set of input molecule conformations that can include different molecules, enabling rapid, accurate force field development.

The most stable fullerene structures from C_{20} to C_{60} are chosen to study the energetics and geometrical consequences of encapsulating the rare gas elements He, Ne, or Ar inside the fullerene cage using dispersion corrected density functional theory. An exponential increase in stability is found with increasing number of carbon atoms. A similar exponential law is found for the volume expansion of the cage due to rare gas encapsulation with decreasing number of carbon atoms. We show that dispersion interactions become important with increasing size of the fullerene cage, where Van der Waals forces between the rare gas atom and the fullerene cage start to dominate over repulsive interactions. The smallest fullerenes where encapsulation of a rare gas element is energetically still favorable are He@C_{48}, Ne@C_{52}, and Ar@C_{58}. While dispersion interactions follow the trend Ar > Ne > He inside C_{60} due to the trend in the rare gas dipole polarizabilities, repulsive forces become soon dominant with smaller cage size and we have a complete reversal for the energetics of rare gas encapsulation at C_{50}. © 2014 Wiley Periodicals, Inc.

Dispersion interactions are essential for a density functional treatment of rare gas encapsulation into fullerene cages. A systematic DFT study using Grimme's dispersion correction for fullerenes from C_{20} to C_{60} shows that rare gas element enclosure becomes energetically favorable only at He@C_{48}, Ne@C_{52}, and Ar@C_{58}.

The Outlier FLOODing method (OFLOOD) is proposed as an efficient conformational sampling method to extract biologically rare events such as protein folding. In OFLOOD, sparse distributions (outliers in the conformational space) were regarded as relevant states for the transitions. Then, the transitions were enhanced through conformational resampling from the outliers. This evidence indicates that the conformational resampling of the sparse distributions might increase chances for promoting the transitions from the outliers to other meta-stable states, which resembles a conformational flooding from the outliers to the neighboring clusters. OFLOOD consists of (i) detections of outliers from conformational distributions and (ii) conformational resampling from the outliers by molecular dynamics (MD) simulations. Cycles of (i) and (ii) are simply repeated. As demonstrations, OFLOOD was applied to folding of Chignolin and HP35. In both cases, OFLOOD automatically extracted folding pathways from unfolded structures with ns-order computational costs, although µs-order canonical MD failed to extract them. © 2014 Wiley Periodicals, Inc.

The Outlier FLOODing method (OFLOOD) is proposed as an efficient conformational sampling method to extract biologically rare events such as protein folding. OFLOOD consists of (i) detections of outliers from conformational distributions and (ii) conformational resampling from the outliers by MD simulations. As demonstrations, OFLOOD was applied to folding of Chignolin and HP35. In both cases, OFLOOD automatically extracted folding pathways from unfolded structures with ns-order computational costs, although µs-order canonical MD failed to extract them.

Consider the network of all secondary structures of a given RNA sequence, where nodes are connected when the corresponding structures have base pair distance one. The expected degree of the network is the average number of neighbors, where average may be computed with respect to the either the uniform or Boltzmann probability. Here, we describe the first algorithm, **RNAexpNumNbors**, that can compute the expected number of neighbors, or expected network degree, of an input sequence. For RNA sequences from the Rfam database, the expected degree is significantly less than the constrained minimum free energy structure, defined to have minimum free energy (MFE) over all structures consistent with the Rfam consensus structure. The expected degree of structural RNAs, such as purine riboswitches, paradoxically appears to be smaller than that of random RNA, yet the difference between the degree of the MFE structure and the expected degree is larger than that of random RNA. Expected degree does not seem to correlate with standard structural diversity measures of RNA, such as positional entropy and ensemble defect. The program **RNAexpNumNbors** is written in C, runs in cubic time and quadratic space, and is publicly available at http://bioinformatics.bc.edu/clotelab/RNAexpNumNbors. © 2014 Wiley Periodicals, Inc.

The first efficient dynamic programming algorithm is presented to compute the expected network degree, for the exponentially large network of all secondary structures of a given RNA sequence. The program RNAexpNumNbors is written in C, runs in cubic time and quadratic space, can compute the expected number of neighbors, or expected network degree, of an input sequence, and is publicly available.

This study spotlights the fundamental insights about the structure and static first hyperpolarizability (*β*) of a series of 2,4-dinitrophenol derivatives (1–5), which are designed by novel bridging core modifications. The central bridging core modifications show noteworthy effects to modulate the optical and nonlinear optical properties in these derivatives. The derivative systems show significantly large amplitudes of first hyperpolarizability as compared to parent system **1**, which are 4, 46, 66, and 90% larger for systems **2, 3, 4**, and **5**, respectively, at Moller–Plesset (MP2)/6-31G* level of theory. The static first hyperpolarizability and frequency dependent coupled-perturbed Kohn–Sham first hyperpolarizability are calculated by means of MP2 and density functional theory methods and compared with respective experimental values wherever possible. Using two-level model with full-set of parameters dependence of transition energy (Δ*Ε*), transition dipole moment (*μ*^{0}) as well as change in dipole moment from ground to excited state (Δ*μ*), the origin of increase in *β* amplitudes is traced from the change in dipole moment from ground to excited state. The causes of change in dipole moments are further discovered through sum of Mulliken atomic charges and intermolecular charge transfer spotted in frontier molecular orbitals analysis. Additionally, analysis of conformational isomers and UV-Visible spectra has been also performed for all designed derivatives. Thus, our present investigation provides novel and explanatory insights on the chemical nature and origin of intrinsic nonlinear optical (NLO) properties of 2,4-dinitrophenol derivatives. © 2014 Wiley Periodicals, Inc.

A fundamental quantum chemical structure–property relationship spotlights the surprising effect of bridging core modification to robust nonlinear optical properties of dinitrophenol derivatives.

A new hybrid MPI/OpenMP parallelization scheme is introduced for the Effective Fragment Potential (EFP) method implemented in the *libefp* software library. The new implementation employs dynamic load balancing algorithm that uses a master/slave model. The software shows excellent parallel scaling up to several hundreds of CPU-cores across multiple nodes. The code uses functions only from the well-established MPI-1 standard that simplifies portability of the library. This new parallel EFP implementation greatly expands the applicability of the EFP and QM/EFP methods by extending attainable time- and length-scales. © 2014 Wiley Periodicals, Inc.

A new hybrid MPI/OpenMP parallelization scheme is introduced for the Effective Fragment Potential (EFP) method implemented in the *libefp* software library. The new implementation employs dynamic load balancing that uses a master/slave model. This new parallel EFP implementation greatly expands the applicability of the EFP and QM/EFP methods by extending attainable time- and length-scales.