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.

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. Our program, Paramfit, 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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Coarse-grained models with short-ranged and anisotropic interactions have recently gained significant attention from the soft matter and biophysics community. The models are being increasingly used for the investigation of biological macromolecules, self-assembly processes, and for the synthesis of new materials. On page 1 (DOI: 10.1002/jcc.23763), Lorenzo Rovigatti, Petr Šulc, István Z. Reguly, and Flavio Romano, show that molecular dynamics simulations of these systems on GPUs can greatly benefit from an unconventional edge-based algorithm. The cover represents a sketch of the method for a system of patchy particles.

On page 49 (DOI: 10.1002/jcc.23771), Chengfei Yan and Xiaoqin Zou describe a novel computational approach, ACCLUSTER, to predict peptide binding sites on protein surfaces by clustering chemical interactions. The method is assessed by diverse proteinpeptide complexes, yielding very good performance. The method does not involve any training database, and can be easily extended to other systems, such as RNA-peptide interactions, for which experimental structural data are insufficient for informatics-based modeling. The cover shows an example (pdb: 1CJF) in which ACCLUSTER correctly identifies the peptide binding site as the top prediction. The predicted sites ranked as numbers one, two, and three are colored red, green, and magenta, respectively.

We test the relative performances of two different approaches to the computation of forces for molecular dynamics simulations on graphics processing units. A “vertex-based” approach, where a computing thread is started per particle, is compared to an “edge-based” approach, where a thread is started per each potentially non-zero interaction. We find that the former is more efficient for systems with many simple interactions per particle while the latter is more efficient if the system has more complicated interactions or fewer of them. By comparing computation times on more and less recent graphics processing unit technology, we predict that, if the current trend of increasing the number of processing cores—as opposed to their computing power—remains, the “edge-based” approach will gradually become the most efficient choice in an increasing number of cases. © 2014 Wiley Periodicals, Inc.

A comparison between two parallelization approaches to be used in molecular dynamics simulations on GPUs was performed. A more aggressive edge-based approach, where a thread is started per interaction, is compared to a more standard vertex-based approach where a thread is started per each particle. Three different potential interactions are tested. If the trend of increasing the number of computing units on GPUs is continued, the edge-based approach will become the best choice in an increasing number of cases.

The bulk structure, the relative stability, and the electronic properties of monoclinic, tetragonal, and cubic ZrO_{2} have been studied from a theoretical point of view, through periodic *ab initio* calculations using different Gaussian basis sets together with Hartree–Fock (HF), pure Density Functional Theory (DFT), and mixed HF/DFT schemes as found in hybrid functionals. The role of a *posteriori* empirical correction for dispersion, according to the Grimme D2 scheme, has also been investigated. The obtained results show that, among the tested functionals, PBE0 not only provides the best structural description of the three polymorphs, but it also represents the best compromise to accurately describe both the geometric and electronic features of the oxide. The relative stability of the three phases can also be qualitatively reproduced, as long as thermal contributions to the energy are taken into account. Four low-index ZrO_{2} surfaces [monoclinic (−111), tetragonal (101 and 111), and cubic (111)] have then been studied at this latter level of theory. Surface energies, atomic relaxations, and electronic properties of these surfaces have been computed. The most stable surface is the cubic one, which is associated to small relaxations confined to the outermost layers. It is followed by the monoclinic (−111) and the tetragonal (101), which have very similar surface energies and atomic displacements. The tetragonal (111) was instead found to be, by far, the less stable with large displacements not only for the outermost but also for deeper layers. Through the comparison of different methods and basis sets, this study allowed us to find a reliable and accurate computational protocol for the investigation of zirconia, both in its bulk and surfaces forms, in view of more complex technological applications, such as ZrO_{2} doped with aliovalent oxides as found in solid oxide fuel cells. © 2014 Wiley Periodicals, Inc.

Zirconia is one of the most studied ceramic materials because of the wide range of its technological applications, which include solid oxide fuel cells (SOFCs). Indeed, yttria-stabilized zirconia is the most used electrolyte in high-temperature SOFC. Density functional theory (DFT) calculations are presented on the bulk structures of three ambient pressure polymorphs of zirconia. Calculations were carried out with different DFT models, from which a computational protocol is applied to selected low-index surfaces.

In this work, we report a detailed theoretical investigation of the phase transition of ammonia borane (NH_{3}BH_{3}; AB), from a tetragonal *I*4*mm* (
) phase with disordered orientation of hydrogen to an orthorhombic phase with *Pmn*2_{1} (
) symmetry, as a function of temperature based on Density Functional Theory calculations with semiempirical dispersion potential correction. We define a series of substructures with the NH_{3}BH_{3} moiety always in *C*_{3}* _{v}* symmetry and the partially occupied high temperature state can be described as a continuous transformation between these substructures. To understand the role of the van der Waals corrections to the physical properties, we use the empirical Grimme's dispersion potential correction (PBE-D2). Both Perdew–Burke–Emzerhof (PBE) and PBE-D2 functional yield almost the same energy sequence along the transition path. However, PBE-D2 functional shows obvious advantage in describing the lattice parameters of AB. The rigid rotor harmonic oscillator approximation is used to compute the free energy and the entropies contribution along the transition pathway. With knowledge of free energy surfaces along rotations of the [NH

The phase transition of ammonia borane (NH_{3}BH_{3}), from a tetragonal *I*4*mm* (
) phase with disordered orientation of hydrogen to an orthorhombic phase with *Pmn*2_{1} (
) symmetry, is investigated as a function of temperature, based on density functional theory calculations with semi-empirical dispersion potential correction. A series of substructures are defined and the partially occupied high temperature state can be described as a continuous transformation between these substructures. The total energies with phonon spectrum of each substructure allow the minimal free energy structure at each temperature to be determined explicitly.

The reduction potentials of a tris(2,2′-bipyridinyl)iron (III/II) and iron(III/II) couples complexed with 2,2′-bipyridinyl derivatives in acetonitrile are predicted using density functional theory. The calculation protocol proposed by Kim et al. (Kim, J. Park, Y. S. Lee, J. Comput. Chem. 2013, 34, 2233) showing reliable performance for the reduction potential is used. The four kinds of the functional groups, a methoxy group, a methyl group, a chlorine atom, and a cyanide group, are substituted at the ligands to examine the electronic effect on the reduction potential. Electron donating/withdrawing effect is analyzed by comparing the reduction potential having different substituents at the same position. The influence of the geometrical strain on the reduction potential is investigated. The good correlation between the experimental results and the calculated results is obtained. Not only the general trend, but also the detailed phenomena are correctly reproduced. The maximum deviation from the experimental value is 0.083 V for the methyl substitution at the position 4. The mean absolute error for the seven couples is 0.047 V. The difference of the reduction potential between the chlorine atom substituted at the positions 4 and 5, 0.1 V, is well described. The difference between the CN and the Cl substitution of 0.318 and 0.228 V for the position 4 and 5 is correctly obtained as 0.325 and 0.213 V, respectively. The simple linear relation between the lowest unoccupied molecular orbital (LUMO) energy of the Fe(III) complexes in solution and the calculated reduction potentials is obtained with the *R*^{2} of 0.977. © 2014 Wiley Periodicals, Inc.

The four kinds of functional groups—methoxy, methyl, chlorine atom, and cyanide—are disubstituted at the positions 3, 4, 5, and 6 of a tris(2,2-bipyridinyl)iron(III/II) redox couple in a symmetrical way. The quality of the prediction for the reduction potential are improved by optimizing the solute cavity size. High reduction potential is obtained by introducing the electron withdrawing groups at position 3 or 6. The LUMO energy of the Fe(III) complex in solution has a linear relation with the predicted reduction potential.

1,2-Migration of the phosphano-group to the carbene center in *N*-phosphano functionalized *N*-heterocyclic carbenes has been studied by density functional theory (DFT) calculations. An intramolecular mechanism with a three-center transition state structure seems to be most plausible for the isolated carbenes, while an intermolecular pathway catalyzed by azolium salts may be preferable for a migration proceeding in the course of generating the carbenes *in situ*. Our calculations show that amino-substitution at the phosphorus atom and an enhanced nucleophilicity of the heterocycle scaffold facilitate the phosphorus shift. Calculated singlet-triplet energy gaps do not correlate with thermodynamic stability of the studied carbenes and their disposition toward the 1,2-rearrangement. © 2014 Wiley Periodicals, Inc.

1,2-Phosphorus migration reaction in *N*-phosphano functionalized *N*-heterocyclic carbenes is investigated. The results show that the most appropriate mechanism is the three-center intramolecular pathway.

Short peptides play important roles in cellular processes including signal transduction, immune response, and transcription regulation. Correct identification of the peptide binding site on a given protein surface is of great importance not only for mechanistic investigation of these biological processes but also for therapeutic development. In this study, we developed a novel computational approach, referred to as ACCLUSTER, for predicting the peptide binding sites on protein surfaces. Specifically, we use the 20 standard amino acids as probes to globally scan the protein surface. The poses forming good chemical interactions with the protein are identified, followed by clustering with the density-based spatial clustering of applications with noise technique. Finally, these clusters are ranked based on their sizes. The cluster with the largest size is predicted as the putative binding site. Assessment of ACCLUSTER was performed on a diverse test set of 251 nonredundant protein–peptide complexes. The results were compared with the performance of POCASA, a pocket detection method for ligand binding site prediction. Peptidb, another protein–peptide database that contains both bound structures and unbound or homologous structures was used to test the robustness of ACCLUSTER. The performance of ACCLUSTER was also compared with PepSite2 and PeptiMap, two recently developed methods developed for identifying peptide binding sites. The results showed that ACCLUSTER is a promising method for peptide binding site prediction. Additionally, ACCLUSTER was also shown to be applicable to nonpeptide ligand binding site prediction. © 2014 Wiley Periodicals, Inc.

A new computational method is developed to predict peptide binding sites on protein surfaces by clustering chemical interactions. The method has been assessed by diverse protein–peptide complexes and achieved encouraging performance in the identification of peptide binding sites. The method can also be used as an alternative for prediction of ligand binding pockets. The algorithm can be easily generalized to predict peptide-RNA binding sites.

Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms—Random Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. © 2014 Wiley Periodicals, Inc.

An easy-to-use web tool to mine the PubChem BioAssay database and develop novel structure activity models based on modern machine learning approaches.