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 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 the position 3 or 6. The LUMO energy of Fe(III) complex in solution has the linear relation with the predicted reduction potential.

Förster resonance energy transfer (FRET) measurements are widely used to investigate (bio)molecular interactions or/and association. FRET efficiencies, the primary data obtained from this method, give, in combination with the common assumption of isotropic chromophore orientation, detailed insight into the lengthscale of molecular phenomena. This study illustrates the application of a FRET efficiency restraint during classical atomistic molecular dynamics simulations of a mutant mastoparan X peptide in either water or 7 M aqueous urea. The restraint forces acting on the donor and acceptor chromophores ensure that the sampled peptide configurational ensemble satisfies the experimental primary data by modifying interchromophore separation and chromophore transition dipole moment orientations. By means of a conformational cluster analysis, it is seen that indeed different configurational ensembles may be sampled without and with application of the restraint. In particular, while the FRET efficiency and interchromophore distances monitored in an unrestrained simulation may differ from the experimentally-determined values, they can be brought in agreement with experimental data through usage of the FRET efficiency restraining potential. Furthermore, the present results suggest that the assumption of isotropic chromophore orientation is not always justified. The FRET efficiency restraint allows the generation of configurational ensembles that may not be accessible with unrestrained simulations, and thereby supports a meaningful interpretation of experimental FRET results in terms of the underlying molecular degrees of freedom. Thus, it offers an additional tool to connect the realms of computer and wet-lab experimentation. © 2014 Wiley Periodicals, Inc.

This work describes how a special restraint potential energy term can be used in molecular dynamics simulations of a system undergoing Förster resonance energy transfer (FRET) to bring the simulated FRET efficiency in agreement with the FRET efficiency measured in experiment. Thus, the methodology allows the generation of configurational ensembles that may not be accessible with unrestrained simulations, and thereby supports a meaningful interpretation of experimental FRET results in terms of the underlying molecular degrees of freedom (interchromophore distances and orientations).

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, including 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.

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.

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 de 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.

LOOS (Lightweight Object Oriented Structure-analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool-writer. In addition, LOOS is bundled with over 140 prebuilt tools, including suites of tools for analyzing simulation convergence, three-dimensional histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only four core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development. © 2014 Wiley Periodicals, Inc.

LOOS is a software library designed to facilitate making novel tools for analyzing molecular dynamics simulations using C++ or Python. LOOS supports reading the native file formats of most common biomolecular simulation packages. A dynamic atom selection language is included and is easily accessible to the tool-writer. LOOS is bundled with over 140 tools. Through modern C++ design, LOOS is both simple to develop with and is easily extensible

Olfactory receptors (ORs) represent the largest subfamily of the superfamily G protein-coupled receptors (GPCRs). This family of membrane receptors functions as essential gateway for activation of many cellular signaling pathways. Finding universal principles underlying GPCR activation by studying ORs is important for the design of new therapeutics that target olfaction-related and other GPCR-malfunctioning diseases. In addition, gaining knowledge regarding the interactions between ORs and their cognate ligands (odorants) may contribute to solve the puzzle of how odor perception is encoded in humans. As no crystal structure of an OR is available yet, homology modeling can be applied to generate a three-dimensional OR model. Molecular docking, molecular dynamics simulations and qualitative structure-activity-relationship can further guide experimental research by investigating interactions at the atomic level. This article will review these computational techniques as well as present databases and popular software suites, which can support researchers in the OR research field. © 2014 Wiley Periodicals, Inc.

G protein-coupled receptors (GPCRs) compose one of the largest protein membrane family in our body. These refined receptors have a critical function in many essential regulation pathways and thus are involved in several severe diseases. Therefore, many studies are focus to gain insight in their functioning. In this review, Olfactory receptors (ORs), the largest GPCR subfamily, are discussed with main focus on their structural characteristics and the computational techniques that can be used to broaden our current knowledge regarding both GPCRs-malfunctioning diseases and human odor perception.

The semiexperimental (SE) technique, whereby equilibrium rotational constants are derived from experimental ground-state rotational constants and corrections based on an *ab initio* cubic force field, has the reputation to be one of the most accurate methods to determine an equilibrium structure (
). However, in some cases, it cannot determine accurately the position of the hydrogen. To investigate the origins of this difficulty, the SE structures of several molecules containing either the OH or the CH_{3} group are determined and compared to their best *ab initio* counterparts. It appears that an important factor is the accuracy of the geometry used to calculate the force field, in particular when the least-squares system is not well conditioned. In this case, the mixed regression method is often an easy way to circumvent this difficulty. © 2014 Wiley Periodicals, Inc.

The semiexperimental (SE) technique has the reputation to be one of the most accurate methods to determine an equilibrium structure. However, in some cases, it cannot accurately determine the position of the hydrogen atoms in a methyl or hydroxyl group. To investigate the origins of this difficulty, the SE structures of several molecules containing either the OH or the CH3 group are determined and compared to their best *ab initio* counterparts.

A novel approach for the selection of step parameters as reaction coordinates in enhanced sampling simulations of DNA is presented. The method uses three atoms per base and does not require coordinate overlays or idealized base pairs. This allowed for a highly efficient implementation of the calculation of all step parameters and their Cartesian derivatives in molecular dynamics simulations. Good correlation between the calculated and actual twist, roll, tilt, shift, and slide parameters is obtained, while the correlation with rise is modest. The method is illustrated by its application to the methylated and unmethylated 5′-CATGTGACGTCACATG-3′ double stranded DNA sequence. One-dimensional umbrella simulations indicate that the flexibility of the central CG step is only marginally affected by methylation. © 2014 Wiley Periodicals, Inc.

A simplified method for the calculation of DNA step parameters and their Cartesian derivatives is introduced. Using three atoms per base and no structure overlays, the method is highly efficient for use in free energy simulations while retaining good accuracy. The method is illustrated by calculating the flexibility of the central CG step in methylated and unmethylated DNA strands.

The potential energy surfaces (PES) of a series of gold–boron clusters with formula Au* _{n}*B (

The potential energy surfaces of gold clusters doped with one and two boron atoms have been explored in detail using a stochastic search algorithm. DFT computations show that these gold-boron clusters have well-defined growth patterns.

On page 2272 (DOI: 10.1002/jcc.23752), Jorge Garza and co-workers report an efficient grid-based algorithm to find critical points on the electron density, which scales very well on CPUs and exhibits a high performance on GPUs. The convenience in using this new proposal is evidenced when non-nuclear attractors are found in a molecule and when the code is used on common GPUs, which are nondedicated to high-performance applications. The cover was designed by Alfredo Garza.

Damien J. Carter and Andrew L. Rohl investigate the performance of several van der Waals (vdW) functionals at calculating the interactions between benzene and the copper (111) surface. On page 2263 (DOI: 10.1002/jcc.23745), they demonstrate that local orbital methods using appropriate basis sets combined with a vdW functional can successfully model adsorption between metal surfaces and organic molecules.

The thermal stabilities and melting behavior of icosahedral nickel clusters under hydrostatic pressure have been studied by constant-pressure molecular dynamics simulation. The potential energy and Lindemann index are calculated. The overall melting temperature exhibits a strong dependence on pressure. The Lindemann index of solid structure before melting varies slowly and is almost independent of pressure. However, after the clusters melt completely, the Lindemann index at the overall melting point strongly depends on pressure. The overall melting temperature is found to be increasing nonlinearly with increasing pressure, while the volume change during melting decreases linearly with increasing pressure. Under a high pressure and temperature environment, similar angular distributions were found between liquid and solid structures, indicating the existence of a converging local structure. © 2014 Wiley Periodicals, Inc.

The nickel–iron mixture is a dominant component in the terrestrial planet lower mantle, which makes the melting of nickel under hydrostatic pressure of interest. Here the melting behaviors of icosahedral nickel clusters under hydrostatic pressure are studied by constant-pressure molecular dynamic simulation. This work intends to provide a better understanding of the thermal properties of nickel clusters and will aid development of new nanomaterials under hydrostatic pressure.

Hydrogen interstitials in austenitic Fe-Mn alloys were studied using density-functional theory to gain insights into the mechanisms of hydrogen embrittlement in high-strength Mn steels. The investigations reveal that H atoms at octahedral interstitial sites prefer a local environment containing Mn atoms rather than Fe atoms. This phenomenon is closely examined combining total energy calculations and crystal orbital Hamilton population analysis. Contributions from various electronic phenomena such as elastic, chemical, and magnetic effects are characterized. The primary reason for the environmental preference is a volumetric effect, which causes a linear dependence on the number of nearest-neighbour Mn atoms. A secondary electronic/magnetic effect explains the deviations from this linearity. © 2014 Wiley Periodicals, Inc.

Adding a substantial amount of manganese to steels yields a material with extraordinary mechanical properties. A tiny amount of hydrogen in high-Mn steels, however, is already suffcient for the onset of devastating embrittlement effects. Using first-principles methods, an attraction of both elements is revealed, providing a complete analysis of the elastic, chemical, and magnetic origin of this phenomenon. These insights contribute to strategies to better control the hydrogen distribution in steels.

The generalized Newton–Euler inverse mass operator (GNEIMO) method is an advanced method for internal coordinates molecular dynamics (ICMD). GNEIMO includes several theoretical and algorithmic advancements that address longstanding challenges with ICMD simulations. In this article, we describe the GneimoSim ICMD software package that implements the GNEIMO method. We believe that GneimoSim is the first software package to include advanced features such as the equipartition principle derived for internal coordinates, and a method for including the Fixman potential to eliminate systematic statistical biases introduced by the use of hard constraints. Moreover, by design, GneimoSim is extensible and can be easily interfaced with third party force field packages for ICMD simulations. Currently, GneimoSim includes interfaces to LAMMPS, OpenMM, and Rosetta force field calculation packages. The availability of a comprehensive Python interface to the underlying C++ classes and their methods provides a powerful and versatile mechanism for users to develop simulation scripts to configure the simulation and control the simulation flow. GneimoSim has been used extensively for studying the dynamics of protein structures, refinement of protein homology models, and for simulating large scale protein conformational changes with enhanced sampling methods. GneimoSim is not limited to proteins and can also be used for the simulation of polymeric materials.

This paper describes the modular architecture of the GneimoSim software package for performing long time scale internal coordinate molecular dynamics simulations. GneimoSim includes advanced dynamics methods, integrators for robust long time scale dynamics, interfaces for all-atom forcefields such as AMBER and CHARMM, and the Generalized Born solvation model. The software is available at no cost for academic use.

An important task of biomolecular simulation is the calculation of relative binding free energies upon chemical modification of partner molecules in a biomolecular complex. The potential of mean force (PMF) along a reaction coordinate for association or dissociation of the complex can be used to estimate binding affinities. A free energy perturbation approach, termed umbrella sampling (US) perturbation, has been designed that allows an efficient calculation of the change of the PMF upon modification of a binding partner based on the trajectories obtained for the wild type reference complex. The approach was tested on the interaction of modified water molecules in aqueous solution and applied to *in silico* alanine scanning of a peptide-protein complex. For the water interaction test case, excellent agreement with an explicit PMF calculation for each modification was obtained as long as no long range electrostatic perturbations were considered. For the alanine scanning, the experimentally determined ranking and binding affinity changes upon alanine substitutions could be reproduced within 0.1–2.0 kcal/mol. In addition, good agreement with explicitly calculated PMFs was obtained mostly within the sampling uncertainty. The combined US and perturbation approach yields, under the condition of sufficiently small system modifications, rigorously derived changes in free energy and is applicable to any PMF calculation. © 2014 Wiley Periodicals, Inc.

The change of a potential of mean force upon the modification of a system can be estimated by an umbrella sampling perturbation method that does not require additional simulations. Application to computational alanine-scanning of a peptide-protein complex by means of relative separation of potential of mean forces (PMFs) resulted in accurate free energy estimates for a series of peptide modifications. The method yields rigorously derived free energy changes under the condition of sufficiently small perturbations.

We investigate the performance of several van der Waals (vdW) functionals at calculating the interactions between benzene and the copper (111) surface, using the local orbital approach in the SIESTA code. We demonstrate the importance of using surface optimized basis sets to calculate properties of pure surfaces, including surface energies and the work function. We quantify the errors created using (3 × 3) supercells to study adsorbate interactions using much larger supercells, and show non-negligible errors in the binding energies and separation distances. We examine the eight high-symmetry orientations of benzene on the Cu (111) surface, reporting the binding energies, separation distance, and change in work function. The optimized vdW-DF(optB88-vdW) functional provides superior results to the vdW-DF(revPBE) and vdW-DF2(rPW86) functionals, and closely matches the experimental and experimentally deduced values. This work demonstrates that local orbital methods using appropriate basis sets combined with a vdW functional can model adsorption between metal surfaces and organic molecules.

The performance of several van der Waals (vdW) functionals at calculating the interactions between benzene and the copper (111) surface was investigated. Local orbital methods using appropriate basis sets combined with a vdW functional can successfully model adsorption between metal surfaces and organic molecules.

Using a grid-based method to search the critical points in electron density, we show how to accelerate such a method with graphics processing units (GPUs). When the GPU implementation is contrasted with that used on central processing units (CPUs), we found a large difference between the time elapsed by both implementations: the smallest time is observed when GPUs are used. We tested two GPUs, one related with video games and other used for high-performance computing (HPC). By the side of the CPUs, two processors were tested, one used in common personal computers and other used for HPC, both of last generation. Although our parallel algorithm scales quite well on CPUs, the same implementation on GPUs runs around 10× faster than 16 CPUs, with any of the tested GPUs and CPUs. We have found what one GPU dedicated for video games can be used without any problem for our application, delivering a remarkable performance, in fact; this GPU competes against one HPC GPU, in particular when single-precision is used. © 2014 Wiley Periodicals, Inc.

Grid-based methods are quite convenient to search for critical points on systems that exhibit non-nuclear attractors. However, these methods are computationally expensive. An efficient algorithm with good scaling on central processing units is proposed. The algorithm has better performance when implemented on graphics processing units (GPUs), even in GPUs not dedicated for high-performance computing.