The relative stability of biologically relevant, hydrogen bonded complexes with shortened distances can be assessed at low cost by the electrostatic multipole term alone more successfully than by ab initio methods. These results imply that atomic multipole moments may help improve ligand–receptor ranking predictions, particularly in cases where accurate structural data are not available. © 2013 Wiley Periodicals, Inc.

We appreciate the interest of Dr. Rayne on our article and we completely agree that the dataset of (benzo-)triazoles, which were screened by the hydroxyl radical reaction quantitative structure-activity relationship (QSAR) model, was not only composed of benzo-triazoles but also included some simpler triazoles (without the condensed benzene ring), such as the chemicals listed by Dr. Rayne, as well as some related heterocycles (also few not aromatic). We want to clarify that in this article (as well as in other articles in which the same dataset was screened), for conciseness, the abbreviations (B)TAZs and BTAZs were used as general (and certainly too simplified) notations meaning an extended dataset of benzo-triazoles, triazoles, and related compounds. © 2013 Wiley Periodicals, Inc.

We present a theoretical development of the equations required to perform an analytic geometry optimization of a molecular system using the XYG3 type of doubly hybrid (xDH) functionals. In contrast to the well-established B2PLYP type of DH functionals, the energy expressions in the xDH functionals are constructed by using density and orbital information from another standard Kohn–Sham (KS) functional (e.g., B3LYP) for doing the self-consistent field calculations. Thus, the xDH functionals are nonvariational in both the hybrid density functional part and the second-order perturbation part, each of which requires formally to solve a coupled-perturbed KS equation. An implementation is reported here which combines the two parts by defining a total Lagrangian such that only a single set of the Z-vector equations need to be solved. The computational cost with our implementation is of the same order as those for the conventional Møller–Plesset theory to the second order (MP2) and B2PLYP. Systematic test calculations are provided for covalently bonded molecules as well as compounds involving the intramolecular nonbonded interactions for the main group elements. Satisfactory performance of the xDH functionals demonstrates that the extra computer time on top of the conventional KS procedure is well-invested, in particular, when the standard KS functionals and MP2 as well, are problematic. © 2013 Wiley Periodicals, Inc.

Targeted therapy is currently a hot topic in the fields of cancer research and drug design. An important requirement for this approach is the development of potent and selective inhibitors for the identified target protein. However, current ways to estimate inhibitor efficacy rely on empirical protein–ligand interaction scoring functions which, suffering from their heavy parameterizations, often lead to a low accuracy. In this work, we develop a nonfitting scoring function, which consists of three terms: (1) gas-phase protein-ligand binding enthalpy obtained by the eXtended ONIOM hybrid method based on an integration of density functional theory (DFT) methods (XYG3 and ωB97X-D) and the semiempirical PM6 method, (2) solvation free energy based on DFT-SMD solvation model, and (3) entropy effect estimated by using DFT frequency analysis. The new scoring function is tested on a cyclin-dependent kinase 2 (CDK2) inhibitor database including 76 CDK2 protein inhibitors and a p21-activated kinase 1 (PAK1) inhibitor database including 20 organometallic PAK1 protein inhibitors. From the results, good correlations are found between the calculated scores and the experimental inhibitor efficacies with the square of correlation coefficient R² of 0.76–0.88. This suggests a good predictive power of this scoring function. To the best of our knowledge, this is the first high level theory-based nonfitting scoring function with such a good level of performance. This scoring function is recommended to be used in the final screening of lead structure derivatives. © 2013 Wiley Periodicals, Inc.

O1s core-electron binding energies (CEBE) of the atomic oxygens on different Ag surfaces were investigated by the symmetry adapted cluster-configuration interaction (SAC-CI) method combined with the dipped adcluster model, in which the electron exchange between bulk metal and adsorbate is taken into account properly. Electrophilic and nucleophilic oxygens (O_elec and O_nuc) that might be important for olefin epoxidation in a low-oxygen coverage condition were focused here. We consider the O1s CEBE as a key property to distinguish the surface oxygen states, and series of calculation was carried out by the Hartree–Fock, Density functional theory, and SAC/SAC-CI methods. The experimental information and our SAC/SAC-CI results indicate that O_elec is the atomic oxygen adsorbed on the fcc site of Ag(111) and that O_nuc is the one on the reconstructed added-row site of Ag(110) and that one- and two-electron transfers occur, respectively, to the O_elec and O_nuc adclusters from the silver surface. © 2013 Wiley Periodicals, Inc.

A set of exchange-correlation functionals, including BLYP, PBE0, B3LYP, BHandHLYP, CAM-B3LYP, LC-BLYP, and HSE, has been used to determine static and dynamic nonresonant (nuclear relaxation) vibrational (hyper)polarizabilities for a series of all-trans polymethineimine (PMI) oligomers containing up to eight monomer units. These functionals are assessed against reference values obtained using the Møller–Plesset second-order perturbation theory (MP2) and CCSD methods. For the smallest oligomer, CCSD(T) calculations confirm the choice of MP2 and CCSD as appropriate for assessing the density functionals. By and large, CAM-B3LYP is the most successful, because it is best for the nuclear relaxation contribution to the static linear polarizability, intensity-dependent refractive index second hyperpolarizability, static second hyperpolarizability, and is close to the best for the electro-optical Pockels effect first hyperpolarizability. However, none of the functionals perform satisfactorily for all the vibrational (hyper)polarizabilities studied. In fact, in the case of electric field-induced second harmonic generation all of them, as well as the Hartree–Fock approximation, yield the wrong sign. We have also found that the Pople 6–31+G(d) basis set is unreliable for computing nuclear relaxation (hyper)polarizabilities of PMI oligomers due to the spurious prediction of a nonplanar equilibrium geometry. © 2013 Wiley Periodicals, Inc.

A quantum chemical method based on a Hartree-Fock calculation with a small Gaussian AO basis set is presented. Its main area of application is the computation of structures, vibrational frequencies, and noncovalent interaction energies in huge molecular systems. The method is suggested as a partial replacement of semiempirical approaches or density functional theory (DFT) in particular when self-interaction errors are acute. In order to get accurate results three physically plausible atom pair-wise correction terms are applied for London dispersion interactions (D3 scheme), basis set superposition error (gCP scheme), and short-ranged basis set incompleteness effects. In total nine global empirical parameters are used. This so-called Hartee-Fock-3c (HF-3c) method is tested for geometries of small organic molecules, interaction energies and geometries of noncovalently bound complexes, for supramolecular systems, and protein structures. In the majority of realistic test cases good results approaching large basis set DFT quality are obtained at a tiny fraction of computational cost. © 2013 Wiley Periodicals, Inc.

The cytochromes P450 constitute a ubiquitous family of metalloenzymes, catalyzing manifold reactions of biological and synthetic importance via a thiolate-ligated iron-oxo (IV) porphyrin radical species denoted compound I (Cpd I). Experimental investigations have implicated this intermediate in a broad spectrum of biophysically interesting phenomena, further augmenting the importance of a Cpd I model system. Ab initio molecular dynamics, including Car–Parrinello and path integral methods, conjoin electronic structure theory with finite temperature simulation, affording tools most valuable to approach such enzymes. These methods are typically driven by density functional theory (DFT) in a plane-wave pseudopotential framework; however, existing studies of Cpd I have been restricted to localized Gaussian basis sets. The appropriate choice of density functional and pseudopotential for such simulations is accordingly not obvious. To remedy this situation, a systematic benchmarking of thiolate-ligated Cpd I is performed using several generalized-gradient approximation (GGA) functionals in the Martins–Troullier and Vanderbilt ultrasoft pseudopotential schemes. The resultant electronic and structural parameters are compared to localized–basis DFT calculations using GGA and hybrid density functionals. The merits and demerits of each scheme are presented in the context of reproducing existing experimental and theoretical results for Cpd I. © 2013 Wiley Periodicals, Inc.

The quantum mechanics (QM) and quasiclassical trajectory (QCT) calculations have been carried out for the title reaction with the ground minimal allowed rotational state of CH (j = 1) on the 1 ¹A′ potential energy surface. For the reaction probability at total angular momentum J = 0, a similar trend of the QM and QCT calculations is observed, and the QM results are larger than the latter almost in the whole considered energy range (0.1–1.5 eV). The QCT integral cross sections are larger than the QM results with centrifugal sudden approximation, while smaller than those from QM method including Coriolis coupling for collision energies bigger than 0.25 eV. The quantum wave-packet computations show that the Coriolis coupling effects get more and more pronounced with increasing of J. In addition to the scalar properties, the stereodynamical properties, such as the average rotational alignment factor <P₂(j′•k)>, the angular distributions P(θ_r), P(ϕ_r), P(θ_r,ϕ_r), and the polarization-dependent generalized differential cross sections have been explored in detail by QCT approach. © 2013 Wiley Periodicals, Inc.

To facilitate computational study of proteins in the AlkB family and related α-ketoglutarate/Fe(II)-dependent dioxygenases, we have tested a simple modeling strategy for the non-heme Fe(II) site in which the iron is represented by a simple +2 point charge with Lennard-Jones parameters. Calculations for an AlkB active site model in the gas phase and ∼150 ns molecular dynamics (MD) simulations for two enzyme-dsDNA complexes (E. coli AlkB-dsDNA and ABH2-dsDNA) suggest that this simple modeling strategy provides a satisfactory description of structural properties of the Fe(II) site in AlkB enzymes, provided that care is exercised to control the binding mode of carboxylate (Asp) to the iron. MD simulations using the model for AlkB-dsDNA and ABH2-dsDNA systems find that although the structural features for the latter are overall in good agreement with the crystal structure, the dsDNA, and AlkB-dsDNA interface undergo substantial changes during the MD simulations from the crystal structure. Even for ABH2, new interactions form between a long loop region and dsDNA upon structural relaxation of the loop, supporting the role of this loop in DNA binding despite the lack of interactions between them in the crystal structure. Analysis of DNA backbone torsional distributions helps identify regions that adopt strained conformations. Collectively, the results highlight that crystal packing may have a significant impact on the structure of protein-DNA complexes; the simulations also provide additional insights regarding why AlkB and ABH2 prefer single-strand and double-strand DNA, respectively, as substrate. © 2013 Wiley Periodicals, Inc.

This article focuses on the development of an approach for ab initio protein structure prediction (PSP) without using any earlier knowledge from similar protein structures, as fragment-based statistics or inference of secondary structures. Such an approach is called purely ab initio prediction. The article shows that well-designed multiobjective evolutionary algorithms can predict relevant protein structures in a purely ab initio way. One challenge for purely ab initio PSP is the prediction of structures with β-sheets. To work with such proteins, this research has also developed procedures to efficiently estimate hydrogen bond and solvation contribution energies. Considering van der Waals, electrostatic, hydrogen bond, and solvation contribution energies, the PSP is a problem with four energetic terms to be minimized. Each interaction energy term can be considered an objective of an optimization method. Combinatorial problems with four objectives have been considered too complex for the available multiobjective optimization (MOO) methods. The proposed approach, called “Multiobjective evolutionary algorithms with many tables” (MEAMT), can efficiently deal with four objectives through the combination thereof, performing a more adequate sampling of the objective space. Therefore, this method can better map the promising regions in this space, predicting structures in a purely ab initio way. In other words, MEAMT is an efficient optimization method for MOO, which explores simultaneously the search space as well as the objective space. MEAMT can predict structures with one or two domains with RMSDs comparable to values obtained by recently developed ab initio methods (GAPF_CG, I-PAES, and Quark) that use different levels of earlier knowledge. © 2013 Wiley Periodicals, Inc.

An accurate single-sheeted double many-body expansion potential energy surface is reported for the title system. A switching function formalism has been used to warrant the correct behavior at the and dissociation channels involving nitrogen in the ground and first excited states. The topographical features of the novel global potential energy surface are examined in detail, and found to be in good agreement with those calculated directly from the raw ab initio energies, as well as previous calculations available in the literature. The novel surface can be using to treat well the Renner–Teller degeneracy of the and states of . Such a work can both be recommended for dynamics studies of the reaction and as building blocks for constructing the double many-body expansion potential energy surface of larger nitrogen/hydrogen-containing systems. In turn, a test theoretical study of the reaction has been carried out with the method of quantum wave packet on the new potential energy surface. Reaction probabilities, integral cross sections, and differential cross sections have been calculated. Threshold exists because of the energy barrier (68.5 meV) along the minimum energy path. On the curve of reaction probability for total angular momentum J = 0, there are two sharp peaks just above threshold. The value of integral cross section increases quickly from zero to maximum with the increase of collision energy, and then stays stable with small oscillations. The differential cross section result shows that the reaction is a typical forward and backward scatter in agreement with experimental measurement result. © 2013 Wiley Periodicals, Inc.

We introduce a class of partial atomic charge assignment method that provides ab initio quality description of the electrostatics of bioorganic molecules. The method uses a set of models that neither have a fixed functional form nor require a fixed set of parameters, and therefore are capable of capturing the complexities of the charge distribution in great detail. Random Forest regression is used to build separate charge models for elements H, C, N, O, F, S, and Cl, using training data consisting of partial charges along with a description of their surrounding chemical environments; training set charges are generated by fitting to the b3lyp/6-31G* electrostatic potential (ESP) and are subsequently refined to improve consistency and transferability of the charge assignments. Using a set of 210 neutral, small organic molecules, the absolute hydration free energy calculated using these charges in conjunction with Generalized Born solvation model shows a low mean unsigned error, close to 1 kcal/mol, from the experimental data. Using another large and independent test set of chemically diverse organic molecules, the method is shown to accurately reproduce charge-dependent observables—ESP and dipole moment—from ab initio calculations. The method presented here automatically provides an estimate of potential errors in the charge assignment, enabling systematic improvement of these models using additional data. This work has implications not only for the future development of charge models but also in developing methods to describe many other chemical properties that require accurate representation of the electronic structure of the system. © 2013 Wiley Periodicals, Inc.

We propose a new algorithm to determine reaction paths and test its capability for Ar₁₂ and Ar₁₃ clusters. Its main ingredient is a search for the local minima on a (n−1) dimensional hyperplane (n = dimension of the complete system in Cartesian coordinates) lying perpendicular to the straight line connection between initial and final states. These minima are part of possible reaction paths and are, hence, used as starting points for an uphill search to the next transition state. First, path fragments are obtained from subsequent relaxations starting from these transition states. They can be combined with information from the straight line connection procedure to obtain complete paths. Our test computations for Ar₁₂ and Ar₁₃ clusters prove that PathOpt delivers several reaction paths in one round. © 2013 Wiley Periodicals, Inc.

Understanding binding mechanisms between enzymes and potential inhibitors and quantifying protein–ligand affinities in terms of binding free energy is of primary importance in drug design studies. In this respect, several approaches based on molecular dynamics simulations, often combined with docking techniques, have been exploited to investigate the physicochemical properties of complexes of pharmaceutical interest. Even if the geometric properties of a modeled protein–ligand complex can be well predicted by computational methods, it is still challenging to rank with chemical accuracy a series of ligand analogues in a consistent way. In this article, we face this issue calculating relative binding free energies of a focal adhesion kinase, an important target for the development of anticancer drugs, with pyrrolopyrimidine-based ligands having different inhibitory power. To this aim, we employ steered molecular dynamics simulations combined with nonequilibrium work theorems for free energy calculations. This technique proves very powerful when a series of ligand analogues is considered, allowing one to tackle estimation of protein–ligand relative binding free energies in a reasonable time. In our cases, the calculated binding affinities are comparable with those recovered from experiments by exploiting the Michaelis–Menten mechanism with a competitive inhibitor.

We present a new software framework for Markov chain Monte Carlo sampling for simulation, prediction, and inference of protein structure. The software package contains implementations of recent advances in Monte Carlo methodology, such as efficient local updates and sampling from probabilistic models of local protein structure. These models form a probabilistic alternative to the widely used fragment and rotamer libraries. Combined with an easily extendible software architecture, this makes PHAISTOS well suited for Bayesian inference of protein structure from sequence and/or experimental data. Currently, two force-fields are available within the framework: PROFASI and OPLS-AA/L, the latter including the generalized Born surface area solvent model. A flexible command-line and configuration-file interface allows users quickly to set up simulations with the desired configuration. PHAISTOS is released under the GNU General Public License v3.0. Source code and documentation are freely available from http://phaistos.sourceforge.net. The software is implemented in C++ and has been tested on Linux and OSX platforms. © 2013 Wiley Periodicals, Inc.

Despite utmost importance in understanding water ionization process, reliable theoretical results of structural changes and molecular dynamics (MD) of water clusters on ionization have hardly been reported yet. Here, we investigate the water cations [(H₂O)_{n = 2–6}⁺] with density functional theory (DFT), Möller–Plesset second-order perturbation theory (MP2), and coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. The complete basis set limits of interaction energies at the CCSD(T) level are reported, and the geometrical structures, electronic properties, and infrared spectra are investigated. The characteristics of structures and spectra of the water cluster cations reflect the formation of the hydronium cation moiety (H₃O⁺) and the hydroxyl radical. Although most density functionals fail to predict reasonable energetics of the water cations, some functionals are found to be reliable, in reasonable agreement with high-level ab initio results. To understand the ionization process of water clusters, DFT- and MP2-based Born-Oppenheimer MD (BOMD) simulations are performed on ionization. On ionization, the water clusters tend to have an Eigen-like form with the hydronium cation instead of a Zundel-like form, based on reliable BOMD simulations. For the vertically ionized water hexamer, the relatively stable (H₂O)₅⁺ (5sL4A) cluster tends to form with a detached water molecule (H₂O). © 2013 Wiley Periodicals, Inc.

To seek for high-performance small molecule donor materials used in heterojunction solar cell, six acceptor–donor–acceptor small molecules based on naphtho[2,3-b:6,7-b′]dithiophene (NDT) units with different acceptor units were designed and characterized using density functional theory and time-dependent density functional theory. Their geometries, electronic structures, photophysical, and charge transport properties have been scrutinized comparing with the reported donor material NDT(TDPP)₂ (TDPP = thiophene-capped diketopyrrolopyrrole). The open circuit voltage (V_oc), energetic driving force(ΔE_L-L), and exciton binding energy (E_b) were also provided to give an elementary understanding on their cell performance. The results reveal that the frontier molecular orbitals of 3–7 match well with the acceptor material PC₆₁BM, and compounds 3–5 were found to exhibit the comparable performances to 1 and show promising potential in organic solar cells. In particular, comparing with 1, system 7 with naphthobisthiadiazole acceptor unit displays broader absorption spectrum, higher V_oc, lower E_b, and similar carrier mobility. An in-depth insight into the nature of the involved excited states based on transition density matrix and charge density difference indicates that all S₁ states are mainly intramolecular charge transfer states with the charge transfer from central NDT unit to bilateral acceptor units, and also imply that the exciton of 7 can be dissociated easily due to its large extent of the charge transfer. In a word, 7 maybe superior to 1 and may act as a promising donor candidate for organic solar cell. © 2013 Wiley Periodicals, Inc.

N-(Pyridin-2-yl)thiazol-2-amine is a versatile chemical functional unit present in many therapeutically important species. Quantum chemical analysis shows that there are six competitive isomeric structures possible for this class of compounds within a relative energy difference of ∼4 kcal/mol. Some of the isomeric structures possess divalent N(I) character. There appears to be a competition between the thiazole and pyridine groups to accommodate the tautomeric hydrogen, and consequently show electron donating property in the structure with R-N←L representation. Details of electron distribution, tautomeric preferences, protonation energy, and divalent N(I) character, and so on, of this class of compounds are presented in this article. Subsequently, upon protonation, (L→N←L)^⊕ character is clearly evident in these moieties as molecular orbital analysis clearly shows two lone pairs of electrons on the central nitrogen, in this system.

A fluctuating charge model for transition metal complexes, based on the Hirshfeld partitioning scheme, spectroscopic energy data from the NIST Atomic Spectroscopy Database and the electronegativity equalization approach, has been developed and parameterized for organic ligands and their high- and low-spin Fe^II and Fe^III, low-spin Co^III and Cu^II complexes, using atom types defined in the Momec force field. Based on large training sets comprising a variety of transition metal complexes, a general parameter set has been developed and independently validated which allows the efficient computation of geometry-dependent charge distributions in the field of transition metal coordination compounds. © 2013 Wiley Periodicals, Inc.

Introduction of ion mobility mass spectrometry (IMS/MS) into the proteomic workflow provides an orthogonal separation to the widely used LC-MS platforms. IMS also provides structural information that could facilitate peptide identification. However, the lack of tools capable of predictive power in a high-throughput fashion makes peptide global profiling quite challenging. To target this issue, a computational workflow was developed based on biophysical principles to predict the collision cross-section area (CCS) of peptides as measured from IMS/MS experiments. Hosted on a web server, it allows the user to input a primary sequence (query) and retrieve information on peptide structure, sequence, and corresponding CCS. The current version is designed to identify peptide sequences up to 23 residues in length, in its higher charge state, based on a match of the molecule m/z and CCS. The protocol was validated against a 128-sequences-dataset and CCS predicted within 2.8% average error. © 2013 Wiley Periodicals, Inc.

Phytochromes constitute one of the six well-characterized families of photosensory proteins in Nature. From the viewpoint of computational modeling, however, phytochromes have been the subject of much fewer studies than most other families of photosensory proteins, which is likely a consequence of relevant high-resolution structural data becoming available only in recent years. In this work, hybrid quantum mechanics/molecular mechanics (QM/MM) methods are used to calculate UV-vis absorption spectra of Deinococcus radiodurans bacteriophytochrome. We investigate how the choice of QM/MM methodology affects the resulting spectra and demonstrate that QM/MM methods can reproduce the experimental absorption maxima of both the Q and Soret bands with an accuracy of about 0.15 eV. Furthermore, we assess how the protein environment influences the intrinsic absorption of the bilin chromophore, with particular focus on the Q band underlying the primary photochemistry of phytochromes. © 2013 Wiley Periodicals, Inc.

Mean-force dynamics (MFD), which is a fictitious dynamics for a set of collective variables on a potential of mean-force, is a powerful algorithm to efficiently explore free-energy landscapes. Recently, we have introduced logarithmic MFD (LogMFD) (Morishita et al., Phys. Rev. E 2012, 85, 066702) which overcomes difficulties encounterd in free-energy calculations using standard approaches such as thermodynamic integration. Here, we present a guide to implementing LogMFD calculations paying attention to the practical issues in choosing the parameters in LogMFD. A primary focus is given to the effect of the parameters on the accuracy of the reconstructed free-energy profiles. A recipe for reducing the errors due to energy dissipation is presented. We also demonstrate that multidimensional free-energy landscapes can be reconstructed on-the-fly using LogMFD, which cannot be accomplished using any other free-energy calculation techniques. © 2013 Wiley Periodicals, Inc.

Due to the significant human effort and chemical intuition required to locate chemical reaction pathways with quantum chemical modeling, only a small subspace of possible reactions is usually investigated for any given system. Herein, a systematic approach is proposed for locating reaction paths that bypasses the required human effort and expands the reactive search space, all while maintaining low computational cost. To achieve this, a range of intermediates are generated that represent potential single elementary steps away from a starting structure. These structures are then screened to identify those that are thermodynamically accessible, and then feasible reaction paths to the remaining structures are located. This strategy for elementary reaction path finding is independent of atomistic model whenever bond breaking and forming are properly described. The approach is demonstrated to work well for upper main group elements, but this limitation can easily be surpassed. Further extension will allow discovery of multistep reaction mechanisms in a single computation. The method is highly parallel, allowing for effective use of modern large-scale computational clusters. © 2013 Wiley Periodicals, Inc.

We present multireference calculations for the characterization of ring inversion and double bond shifting in cyclooctatetraene. The results show that it is necessary to treat the dynamical correlation very accurately to obtain correct values for the barrier heights. This can be done, for example, with multireference configuration interaction or with perturbation theory of third order. However, detailed analysis also shows that already a complete active space self-consistent field treatment describes the processes surprisingly well. Thus, this method could be used as a computationally cheap method, for example, for dynamics simulations. © 2013 Wiley Periodicals, Inc.

Multiple conformations separated by high-energy barriers represent a challenging problem in free-energy calculations due to the difficulties in achieving adequate sampling. We present an application of thermodynamic integration (TI) in conjunction with the local elevation umbrella sampling (LE/US) method to improve convergence in alchemical free-energy calculations. TI-LE/US was applied to the guanosine triphosphate (GTP) to 8-Br-GTP perturbation, molecules that present high-energy barriers between the anti and syn states and that have inverted preferences for those states. The convergence and reliability of TI-LE/US was assessed by comparing with previous results using the enhanced-sampling one-step perturbation (OSP) method. A linear interpolation of the end-state biasing potentials was sufficient to dramatically improve sampling along the chosen reaction coordinate. Conformational free-energy differences were also computed for the syn and anti states and compared to experimental and theoretical results. Additionally, a coupled OSP with LE/US was carried out, allowing the calculation of conformational and alchemical free energies of GTP and 8-substituted GTP analogs. © 2013 Wiley Periodicals, Inc.

We present a novel matrix representation of graphs based on the count of equal-distance common vertices to each pair of vertices in a graph. The element (i, j) of this matrix is defined as the number of vertices at the same distance from vertices (i, j). As illustrated on smaller alkanes, these novel matrices are very sensitive to molecular branching and the distribution of vertices in a graph. In particular, we show that ordered row sums of these novel matrices can facilitate solving graph isomorphism for acyclic graphs. This has been illustrated on all undecane isomers C₁₁H₂₄ having the same path counts (total of 25 molecules), on pair of graphs on 18 vertices having the same distance degree sequences (Slater's graphs), as well as two graphs on 21 vertices having identical several topological indices derived from information on distances between vertices. © 2013 Wiley Periodicals, Inc.

Here, we present just a collection of beans (JACOB): an integrated batch-based framework designed for the rapid development of computational chemistry applications. The framework expedites developer productivity by handling the generic infrastructure tier, and can be easily extended by user-specific scientific code. Paradigms from enterprise software engineering were rigorously applied to create a scalable, testable, secure, and robust framework. A centralized web application is used to configure and control the operation of the framework. The application-programming interface provides a set of generic tools for processing large-scale noninteractive jobs (e.g., systematic studies), or for coordinating systems integration (e.g., complex workflows). The code for the JACOB framework is open sourced and is available at: www.wallerlab.org/jacob. © 2013 Wiley Periodicals, Inc.

We describe principal features of the newly released version, NBO 6.0, of the natural bond orbital analysis program, that provides novel “link-free” interactivity with host electronic structure systems, improved search algorithms and labeling conventions for a broader range of chemical species, and new analysis options that significantly extend the range of chemical applications. We sketch the motivation and implementation of program changes and describe newer analysis options with illustrative applications. © 2013 Wiley Periodicals, Inc.