We address methodological issues in quantum mechanics/molecular mechanics (QM/MM) calculations on a zinc-dependent enzyme. We focus on the first stage of peptide bond cleavage by matrix metalloproteinase-2 (MMP-2), that is, the nucleophilic attack of the zinc-coordinating water molecule on the carbonyl carbon atom of the scissile fragment of the substrate. This step is accompanied by significant charge redistribution around the zinc cation, bond cleavage, and bond formation. We vary the size and initial geometry of the model system as well as the computational protocol to demonstrate the influence of these choices on the results obtained. We present QM/MM potential energy profiles for a set of snapshots randomly selected from QM/MM-based molecular dynamics simulations and analyze the differences in the computed profiles in structural terms. Since the substrate in MMP-2 is located on the protein surface, we investigate the influence of the thickness of the water layer around the enzyme on the QM/MM energy profile. Thin water layers (0–2 Å) give unrealistic results because of structural reorganizations in the active-site region at the protein surface. A 12 Å water layer appears to be sufficient to capture the effect of the solvent; the corresponding QM/MM energy profile is very close to that obtained from QM/MM/SMBP calculations using the solvent macromolecular boundary potential (SMBP). We apply the optimized computational protocol to explain the origin of the different catalytic activity of the Glu116Asp mutant: the energy barrier for the first step is higher, which is rationalized on structural grounds. © 2016 Wiley Periodicals, Inc.

A QM/MM study on the mechanism of peptide cleavage catalyzed by the matrix metalloproteinase type 2 (MMP-2) enzyme addresses a number of methodological issues. This includes the dependence of the QM/MM results on the treatment of the water environment, especially around the solvent-exposed active site.

The popular MARTINI coarse-grained (CG) force field requires the protein structure to be fixed, and is unsuitable for simulating dynamic processes such as protein folding. Here, we examine the feasibility of developing a flexible protein model within the MARTINI framework. The results demonstrate that the MARTINI CG scheme does not properly describe the volume and packing of protein backbone and side chains and leads to excessive collapse without structural restraints in explicit CG water. Combining atomistic protein representation with the MARTINI CG solvent, such as in the PACE model, dramatically improves description of flexible protein conformations. Yet, the CG solvent is insufficient to capture the conformational dependence of protein–solvent interactions, and PACE is unable to properly model context dependent conformational transitions. Taken together, high physical resolution at or near the atomistic level is likely necessary for flexible protein models with explicit, microscopic solvents, and the coarse-graining needs to focus on possible simplification in interaction potentials. © 2016 Wiley Periodicals, Inc.

Low spatial resolution in representing either the protein or solvent molecules results in severe deficiencies in accurate modeling of context-dependent protein conformational transitions. High physical resolution at or near the atomistic level is likely necessary for developing flexible protein models with explicit, microscopic solvents, and the coarse-graining needs to focus on exploiting possible simplification in interaction potentials.

Quantum chemical calculations play an essential role in the elucidation of reaction mechanisms for redox-active metalloenzymes. For example, the cleavage and the formation of covalent bonds can usually not be described only on the basis of experimental information, but can be followed by the calculations. Conversely, there are properties, like reduction potentials, which cannot be accurately calculated. Therefore, computational and experimental data has to be carefully combined to obtain reliable descriptions of entire catalytic cycles involving electron and proton uptake from donors outside the enzyme. Such a procedure is illustrated here, for the reduction of nitric oxide (NO) to nitrous oxide and water in the membrane enzyme, cytochrome c dependent nitric oxide reductase (cNOR). A surprising experimental observation is that this reaction is nonelectrogenic, which means that no energy is conserved. On the basis of hybrid density functional calculations a free energy profile for the entire catalytic cycle is obtained, which agrees much better with experimental information on the active site reduction potentials than previous ones. Most importantly the energy profile shows that the reduction steps are endergonic and that the entire process is rate-limited by high proton uptake barriers during the reduction steps. This result implies that, if the reaction were electrogenic, it would become too slow when the gradient is present across the membrane. This explains why this enzyme does not conserve any of the free energy released. © 2016 Wiley Periodicals, Inc.

Using the example of NO reduction in the cytochrome c dependent enzyme nitric oxide reductase (cNOR) it is shown how a careful combination of computational and experimental data can produce reliable descriptions of entire catalytic cycles. From the energy profile, the reaction mechanism can be determined and basic bioenergetic questions can be answered.

In this article, the convergence of quantum mechanical (QM) free-energy simulations based on molecular dynamics simulations at the molecular mechanics (MM) level has been investigated. We have estimated relative free energies for the binding of nine cyclic carboxylate ligands to the octa-acid deep-cavity host, including the host, the ligand, and all water molecules within 4.5 Å of the ligand in the QM calculations (158–224 atoms). We use single-step exponential averaging (ssEA) and the non-Boltzmann Bennett acceptance ratio (NBB) methods to estimate QM/MM free energy with the semi-empirical PM6-DH2X method, both based on interaction energies. We show that ssEA with cumulant expansion gives a better convergence and uses half as many QM calculations as NBB, although the two methods give consistent results. With 720,000 QM calculations per transformation, QM/MM free-energy estimates with a precision of 1 kJ/mol can be obtained for all eight relative energies with ssEA, showing that this approach can be used to calculate converged QM/MM binding free energies for realistic systems and large QM partitions. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Different methods have been tested to obtain converged ligand-binding energies with quantum mechanical (QM) methods, based on molecular dynamics simulations at the molecular mechanics level. The results indicate that single-step exponential averaging (ssEA) with cumulant expansion (ssEAc) gives more precise results and uses fewer QM calculations than non-Boltzmann Bennett acceptance ratio approaches employing either all data (NBB13) or only two states at each end point (NBB4).

The structural properties and reactivity of iron-sulfur proteins are greatly affected by interactions between the prosthetic groups and the surrounding amino acid residues. Thus, quantum chemical investigations of the structure and properties of protein-bound iron-sulfur clusters can be severely limited by truncation of computational models. The aim of this study was to identify, *a priori*, significant interactions that must be included in a quantum chemical model. Using the [2Fe-2S] accessory cluster of the FeFe-hydrogenase as a demonstrative example with rich electronic structural features, the electrostatic and covalent effects of the surrounding side chains, charged groups, and backbone moieties were systematically mapped through density functional theoretical calculations. Electron affinities, spin density differences, and delocalization indexes from the quantum theory of atoms in molecules were used to evaluate the importance of each interaction. Case studies for hydrogen bonding and charged side-chain interactions were used to develop selection rules regarding the significance of a given protein environmental effect. A set of general rules is proposed for constructing quantum chemical models for iron-sulfur active sites that capture all significant interactions from the protein environment. This methodology was applied to our previously used models in galactose oxidase and the 6Fe-cluster of FeFe-hydrogenase. © 2016 Wiley Periodicals, Inc.

A set of general rules was developed for constructing computational models that capture covalent and electrostatic interactions from protein environment with significance to the structure of transition-metal prosthetic group. The rules were developed from detailed analyses of the spin density, Coulomb potential, vertical ionization energies was carried out for a [2Fe-2S] cluster. Their transferability was evaluated for the H-cluster of the FeFe-hydrogenase and the [Cu-OTyrCys] catalytic centers of the galactose oxidase.

^{29}Si and ^{31}P magnetic-shielding tensors in covalent network solids have been evaluated using periodic and cluster-based calculations. The cluster-based computational methodology employs pseudoatoms to reduce the net charge (resulting from missing co-ordination on the terminal atoms) through valence modification of terminal atoms using bond-valence theory (VMTA/BV). The magnetic-shielding tensors computed with the VMTA/BV method are compared to magnetic-shielding tensors determined with the periodic GIPAW approach. The cluster-based all-electron calculations agree with experiment better than the GIPAW calculations, particularly for predicting absolute magnetic shielding and for predicting chemical shifts. The performance of the DFT functionals CA-PZ, PW91, PBE, rPBE, PBEsol, WC, and PBE0 are assessed for the prediction of ^{29}Si and ^{31}P magnetic-shielding constants. Calculations using the hybrid functional PBE0, in combination with the VMTA/BV approach, result in excellent agreement with experiment. © 2016 Wiley Periodicals, Inc.

^{29}Si and ^{31}P magnetic-shielding tensors in covalent network solids have been evaluated using periodic and cluster-based calculations. The VMTA/BV approach to terminate clusters allows accurate prediction of these tensors. Examination of various functionals shows that hybrid functionals give agreement with experiment.

We report here the development of hybrid quantum mechanics/molecular mechanics (QM/MM) interface between the plane-wave density functional theory based CPMD code and the empirical force-field based GULP code for modeling periodic solids and surfaces. The hybrid QM/MM interface is based on the electrostatic coupling between QM and MM regions. The interface is designed for carrying out full relaxation of all the QM and MM atoms during geometry optimizations and molecular dynamics simulations, including the boundary atoms. Both Born–Oppenheimer and Car–Parrinello molecular dynamics schemes are enabled for the QM part during the QM/MM calculations. This interface has the advantage of parallelization of both the programs such that the QM and MM force evaluations can be carried out in parallel to model large systems. The interface program is first validated for total energy conservation and parallel scaling performance is benchmarked. Oxygen vacancy in *α*-cristobalite is then studied in detail and the results are compared with a fully QM calculation and experimental data. Subsequently, we use our implementation to investigate the structure of rhodium cluster (Rh_{n}; *n* = 2 to 6) formed from Rh(C_{2}H_{4})_{2} complex adsorbed within a cavity of Y-zeolite in a reducible atmosphere of H_{2} gas. © 2016 Wiley Periodicals, Inc.

A highly parallel CPMD/GULP QM/MM Interface is developed here for performing molecular dynamics simulations of periodic solids. Application of this code for studying static and dynamic properties of zeolite supported Rh clusters is also presented.

Selenium based diaryl dichalcogenides are compounds that are receiving attention in organic synthesis as eco-friendly oxidation agents as well as in pharmaceutical chemistry, where, together with tellurium-based derivatives, are appealing drugs mainly for their antioxidant properties. A benchmark study to establish optimal density functional theory (DFT) methods for the description of their molecular and electronic structure as well as for their energetics is presented here. Structural features, such as the orientation of the phenyl rings, as well as energetic aspects, i.e., the chalcogen-chalcogen bond strength, are discussed, with the aim of applying the novel insights to quantum mechanics-based investigations of their reactivity and to facilitate drug design. © 2016 Wiley Periodicals, Inc.

A benchmark study to establish optimal density functional theory (DFT) methods for the description of the structure and energetics of diaryldichalcogenides is performed to allow rigorous mechanistic studies and facilitate antioxidant drug design.

The Python package PDielec is described, which calculates the infrared absorption characteristics of a crystalline material supported in a non-absorbing medium. PDielec post processes solid-state quantum mechanical and molecular mechanical calculations of the phonons and dielectric response of the crystalline material. Using an effective medium method, the package calculates the internal electric field arising from different particle morphologies and calculates the resulting shift in absorption frequency and intensity arising from the coupling between a phonon and the internal field. The theory of the approach is described, followed by a description of the implementation within PDielec. Finally, a section providing several examples of its application is given. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Using an effective medium theory the Python package, PDielec, calculates the infrared absorption of a crystalline material supported in a non-absorbing medium by post processing the output of solid state quantum mechanical and molecular mechanical calculations of the dielectric response. The theory of the approach is described, followed by a description of the implementation within PDielec. Finally a section providing several examples of its application is given.

Quantum chemical methods have been employed to evaluate the possible configurations of the 1:1 and 1:2 HOSO-formic acid complexes and 1:1:1 HOSO-formic acid-water complexes. The first type of complex involves two H bonds, while the other two types comprise three H bonds in a ring. The complexes are relatively stable, with CBS-QB3 computed binding energies of 14.3 kcal mol^{−1}, 23.4 kcal mol^{−1}, and 21.1 kcal mol^{−1} for the lowest-energy structures of the 1:1, 1:2, and 1:1:1 complexes, respectively. Complex formations induce a large spectral red-shift and an enhancement of the IR intensity for the H-bonded OH stretching modes relative to those in the parent monomers. TDDFT calculations of the low-lying electronic excited states demonstrate that the complexes are photochemically quite stable in the troposphere. Small spectral shifts in comparison to the free HOSO radical suggest that the radical and the complexes would not be easily distinguishable using standard UV/vis absorption spectroscopy. © 2016 Wiley Periodicals, Inc.

This study provides the first insight into the stability of complexes involving the HOSO radical, formic acid and water molecules. Complex formation induces a large spectral red-shift and an enhancement of the IR intensity for the H-bonded OH stretching vibrational modes relative to the modes in the parent monomers. The calculations demonstrate that the complexes are photochemically quite stable in the troposphere. The atmospheric relevance of the complexes is analysed by exploring their thermochemical properties.

Structure-based virtual screening usually involves docking of a library of chemical compounds onto the functional pocket of the target receptor so as to discover novel classes of ligands. However, the overall success rate remains low and screening a large library is computationally intensive. An alternative to this “*ab initio*” approach is virtual screening by binding homology search. In this approach, potential ligands are predicted based on similar interaction pairs (similarity in receptors and ligands). SPOT-Ligand is an approach that integrates ligand similarity by Tanimoto coefficient and receptor similarity by protein structure alignment program SPalign. The method was found to yield a consistent performance in DUD and DUD-E docking benchmarks even if model structures were employed. It improves over docking methods (DOCK6 and AUTODOCK Vina) and has a performance comparable to or better than other binding-homology methods (FINDsite and PoLi) with higher computational efficiency. The server is available at http://sparks-lab.org. © 2016 Wiley Periodicals, Inc.

SPOT-Ligand is a fast and effective virtual screening tool by searching for homology in binding pairs. That is, potential ligands are predicted based on similar interaction pairs (similarity in receptors and ligands). The method is found to yield a consistent performance in DUD and DUD-E docking benchmarks even if model structures were employed. It improves over docking methods and has a performance comparable to or better than other binding-homology methods.

Since the discovery of the halogen dance (HD) reaction more than 60 years ago, numerous insights into the mechanism have been unveiled. To date however, the reaction has not been investigated from a theoretical perspective. Density functional theory (DFT) was used to model the potential energy surface linking the starting reagents to the lithiated products for each step in the mechanism using a thiophene substrate. It was found that the lithium-halogen exchange mechanism is critical to understand the HD mechanism in detail and yielded the knowledge that S_{N}2 transition states (TS) are favored over the four-center type for the lithium-bromine exchange steps. The overall driving force for the HD is thermodynamics, while the kinetic factors tightly control the reaction path through temperature. The S_{N}2 lithium-bromide TS are barrierless, except the second, which is the limiting step. Finally, the model for the HD is discovered to be a pseudo-clock type, due to a highly favorable bromide catalysis step and the reformation of 2-bromothiophene. © 2016 Wiley Periodicals, Inc.

A DFT approach reveals the bromide autocatalysis and pseudo-clock nature of the halogen-dance (HD) mechanism with thiophene. Kinetic and thermodynamic calculations find both four-center and S_{N}2 mechanisms; the latter giving barrierless reaction steps. Exploring the lithium-halogen exchange mechanism is critical to understand the complex HD reaction.

Metadynamics (MTD) is a very powerful technique to sample high-dimensional free energy landscapes, and due to its self-guiding property, the method has been successful in studying complex reactions and conformational changes. MTD sampling is based on filling the free energy basins by biasing potentials and thus for cases with flat, broad, and unbound free energy wells, the computational time to sample them becomes very large. To alleviate this problem, we combine the standard Umbrella Sampling (US) technique with MTD to sample orthogonal collective variables (CVs) in a simultaneous way. Within this scheme, we construct the equilibrium distribution of CVs from biased distributions obtained from independent MTD simulations with umbrella potentials. Reweighting is carried out by a procedure that combines US reweighting and Tiwary–Parrinello MTD reweighting within the Weighted Histogram Analysis Method (WHAM). The approach is ideal for a controlled sampling of a CV in a MTD simulation, making it computationally efficient in sampling flat, broad, and unbound free energy surfaces. This technique also allows for a distributed sampling of a high-dimensional free energy surface, further increasing the computational efficiency in sampling. We demonstrate the application of this technique in sampling high-dimensional surface for various chemical reactions using *ab initio* and QM/MM hybrid molecular dynamics simulations. Further, to carry out MTD bias reweighting for computing forward reaction barriers in *ab initio* or QM/MM simulations, we propose a computationally affordable approach that does not require recrossing trajectories. © 2016 Wiley Periodicals, Inc.

Here, we present a technique to sample a high-dimensional free energy landscape as slices by combining umbrella sampling and metadynamics simulation sampling orthogonal coordinates simultaneously. The full free energy surface is then reconstructed by combining these slices using the Weighted Histogram Analysis Method.

Replica Exchange Molecular Dynamics (REMD) method is a powerful sampling tool in molecular simulations. Recently, we made a modification to the standard REMD method. It places some inactive replicas at different temperatures as well as the active replicas. The method completely decouples the number of the active replicas and the number of the temperature levels. In this article, we make a further modification to our previous method. It uses the inactive replicas in a different way. The inactive replicas first sample in their own knowledge-based energy databases and then participate in the replica exchange operations in the REMD simulation. In fact, this method is a hybrid between the standard REMD method and the simulated tempering method. Using different active replicas, one can freely control the calculation quantity and the convergence speed of the simulation. To illustrate the performance of the method, we apply it to some small models. The distribution functions of the replicas in the energy space and temperature space show that the modified REMD method in this work can let the replicas walk freely in both of the two spaces. With the same number of the active replicas, the free energy surface in the simulation converges faster than the standard REMD. © 2016 Wiley Periodicals, Inc.

This article provides a modified replica exchange molecular dynamics method. Active replicas exchange with inactive replicas from the knowledge-based databases in the simulation. Under the condition of the same calculation quantities, the method can produce more accurate free energy results than the standard method.

ORBKIT is a toolbox for postprocessing electronic structure calculations based on a highly modular and portable Python architecture. The program allows computing a multitude of electronic properties of molecular systems on arbitrary spatial grids from the basis set representation of its electronic wavefunction, as well as several grid-independent properties. The required data can be extracted directly from the standard output of a large number of quantum chemistry programs. ORBKIT can be used as a standalone program to determine standard quantities, for example, the electron density, molecular orbitals, and derivatives thereof. The cornerstone of ORBKIT is its modular structure. The existing basic functions can be arranged in an individual way and can be easily extended by user-written modules to determine any other derived quantity. ORBKIT offers multiple output formats that can be processed by common visualization tools (VMD, Molden, etc.). Additionally, ORBKIT possesses routines to order molecular orbitals computed at different nuclear configurations according to their electronic character and to interpolate the wavefunction between these configurations. The program is open-source under GNU-LGPLv3 license and freely available at https://github.com/orbkit/orbkit/. This article provides an overview of ORBKIT with particular focus on its capabilities and applicability, and includes several example calculations. © 2016 Wiley Periodicals, Inc.

ORBKIT is an open-source toolbox for postprocessing electronic structure calculations. Based on a highly modular and portable Python architecture, it comes both as a standalone program and a function library. The program allows computing electronic properties of molecular systems on arbitrary spatial grids from the output of standard quantum chemistry programs.

In this work, we exploit a new formulation of the potential energy and of the related computational procedures, which embodies the coupling between the intra and intermolecular components, to characterize possible propensities of the collision dynamics in energy transfer processes of interest for simulation and control of phenomena occurring in a variety of equilibrium and nonequilibrium environments. The investigation reported in the paper focuses on the prototype CO_{2}–N_{2} system, whose intramolecular component of the interaction is modeled in terms of a many body expansion while the intermolecular component is modeled in terms of a recently developed bonds-as-interacting-molecular-centers' approach. The main advantage of this formulation of the potential energy surface is that of being (a) truly full dimensional (i.e., all the variations of the coordinates associated with the molecular vibrations and rotations on the geometrical and electronic structure of the monomers, are explicitly taken into account without freezing any bonds or angles), (b) more flexible than other usual formulations of the interaction and (c) well suited for fitting procedures better adhering to accurate *ab initio* data and sensitive to experimental arrangement dependent information. Specific attention has been given to the fact that a variation of vibrational and rotational energy has a higher (both qualitative and quantitative) impact on the energy transfer when a more accurate formulation of the intermolecular interaction (with respect to that obtained when using rigid monomers) is adopted. This makes the potential energy surface better suited for the kinetic modeling of gaseous mixtures in plasma, combustion and atmospheric chemistry computational applications. © 2016 Wiley Periodicals, Inc.

When vibrationally excited CO_{2} collides with N_{2}, variations of the molecular dimensions associated with vibrations and rotations modify the selectivity of the energy content disposal. State-specific vibrational transition probabilities P_{vw} obtained from collision trajectories run on our flexible CO_{2}–N_{2} potential are compared with those obtained on a CO_{2}-frozen potential, plotted versus the impact parameter. The comparison tells us that the effect of vibrations on the energy exchange is relevant and takes place at low impact parameters.

To tune the efficiency of organic semiconductor devices it is important to understand limiting factors as trapping mechanisms for excitons or charges. An understanding of such mechanisms deserves an accurate description of the involved electronical states in the given environment. In this study, we investigate how a polarizable surrounding influences the relative positions of electronically excited states of dimers of different perylene dyes. Polarization effects are particularly interesting for these systems, because gas phase computations predict that the CT states lie slightly above the corresponding Frenkel states. A polarizable environment may change this energy order because CT states are thought to be more sensitive to a polarizable surrounding than Frenkel states. A first insight we got via a TD-HF approach in combination with a polarizable continuum model (PCM). These give limited insights because TD-HF overestimates excitation energies of CT states. However, SCS-CC2 approaches, which are sufficiently accurate, cannot easily be used in combination with continuum solvent models. Hence, we developed two approaches to combine gas phase SCS-CC2 results with solvent effects based on TD-HF computations. Their accuracies were finally checked via ADC(2)//COSMO computations. The results show that for perylene dyes a polarizable surrounding alone does not influence the energetic ordering of CT and Frenkel states. Variations in the energy order of the states only result from nuclear relaxation effects after the excitation process. © 2016 Wiley Periodicals, Inc.

The influence of a polarizable surrounding is crucial for photo-induced processes in organic semiconductors. Different approaches comprising continuum methods and explicit solvent models are tested and a method for transferring TD-HF solvatochromic shifts to high-level *ab initio* gas phase calculations is introduced. In addition, the importance of symmetry breaking effects within the solvent shell or the aggregate are investigated.

The currently available force field parameters for modified RNA residues in AMBER show significant deviations in conformational properties from experimental observations. The examination of the transferability of the recently revised torsion parameters revealed that there was an overall improvement in the conformational properties for some of the modifications but the improvements were still insufficient in describing the sugar pucker preferences (*J. Chem. Inf. Model*. **2014,** *54,* 1129–1142). Here, we report an approach for the development and fine tuning of the AMBER force field parameters for 2-thiouridine, 4-thiouridine, and pseudouridine with diverse conformational preferences. The *χ* torsion parameters were reparameterized at the individual nucleoside level. The effect of combining the revised *γ* torsion parameter and modifying the Lennard-Jones *σ* parameters were also tested by directly comparing the conformational preferences obtained from our extensive molecular dynamics simulations with those from experimental observations. © 2016 Wiley Periodicals, Inc.

Accurate and well tested force field parameters for modified RNA residues are necessary for reliable molecular modeling of their mechanisms of action in multifarious biological processes and for designing chemotherapeutic agents. An effective approach for combining the reparameterized dihedral parameters and recalibration of the Lennard-Jones *σ* parameters is presented to develop an accurate set of AMBER parameters for modified uridines. Molecular dynamics simulations with these new parameters showed better convergence with the experimental conformational preferences.

The “methodology discovery” library for quantum and classical dynamics simulations is presented. One of the major foci of the code is on nonadiabatic molecular dynamics simulations with model and atomistic Hamiltonians treated on the same footing. The essential aspects of the methodology, design philosophy, and implementation are discussed. The code capabilities are demonstrated on a number of model and atomistic test cases. It is demonstrated how the library can be used to study methodologies for quantum and classical dynamics, as well as a tool for performing detailed atomistic studies of nonadiabatic processes in molecular systems. The source code and additional information are available on the Web at http://www.acsu.buffalo.edu/~alexeyak/libra/index.html. © 2016 Wiley Periodicals, Inc.

The Libra code provides a diverse functionality for various types of classical and quantum calculations. The major focus is on methods for nonadiabatic quantum dynamics. Both model and fully atomistic simulation are possible. The library's design allows one to easily use it within Python environment: to develop and test novel dynamical methodologies, as well as to perform pragmatic simulations of realistic materials.

Hydrodynamic interactions (HI) are incorporated into Langevin dynamics of the C_{α}-based protein model using the Truncated Expansion approximation (TEA) to the Rotne–Prager–Yamakawa diffusion tensor. Computational performance of the obtained GPU realization demonstrates the model's capability for describing protein systems of varying complexity (10^{2}–10^{5} residues), including biological particles (filaments, virus shells). Comparison of numerical accuracy of the TEA versus exact description of HI reveals similar results for the kinetics and thermodynamics of protein unfolding. The HI speed up and couple biomolecular transitions through cross-communication among protein domains, which result in more collective displacements of structure elements governed by more deterministic (less variable) dynamics. The force-extension/deformation spectra from nanomanipulations *in silico* exhibit sharper force signals that match well the experimental profiles. Hence, biomolecular simulations without HI overestimate the role of tension/stress fluctuations. Our findings establish the importance of incorporating implicit water-mediated many-body effects into theoretical modeling of dynamic processes involving biomolecules. © 2016 Wiley Periodicals, Inc.

Theoretical modeling of dynamic processes involving protein assemblies requires an accurate description of their physico-chemical properties, which, due to the finite rates of these processes, are influenced by hydrodynamic interactions among their structural elements. Hydrodynamic coupling is incorporated into the Cα–based protein model on GPUs using the Truncated Expansion of Rotne–Prager–Yamakawa diffusion tensor. The results of nanomanipulations *in silico* show the importance of implicit water-mediated many-body effects in describing dynamic transitions in protein assemblies.

We have developed and implemented pseudospectral time-dependent density-functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm–Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time-dependent density-functional theory with full linear response (PS-FLR-TDDFT) and within the Tamm–Dancoff approximation (PS-TDA-TDDFT) for G2 set molecules using B3LYP/6-31G*^{*} show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS-FLR-TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS-FLR-TDDFT and best estimations demonstrate that the accuracy of both PS-FLR-TDDFT and PS-TDA-TDDFT. Calculations for a set of medium-sized molecules, including *C _{n}* fullerenes and nanotubes, using the B3LYP functional and 6-31G

Pseudospectral time-dependent density-functional theory provides 19- to 34-fold speedups for *C _{n}* fullerenes with 450 – 1470 basis functions, 11- to 32-fold speedups for nanotubes with 660 – 3180 basis functions, and 9- to 16-fold speedups for organic molecules with 540 – 1340 basis functions compared to conventional method without sacrificing chemical accuracy. On a set of larger molecules with up to 8100 basis functions, it scales as N

In the presence of a static, nonhomogeneous magnetic field, represented by the axial vector
at the origin of the coordinate system and by the polar vector
, assumed to be spatially uniform, the chiral molecules investigated in this paper carry an orbital electronic anapole, described by the polar vector
. The electronic interaction energy of these molecules in nonordered media is a cross term, coupling
and
via
, one third of the trace of the anapole magnetizability *a _{αβ}* tensor, that is,
. Both
and

Since the average anapole magnetizabilities
of the *S* and *R* enantiomers of a chiral molecule, for example, methyl-oxyrane in the graphical abstract, have same magnitude, but opposite sign, also the electronic interaction energies *W*** ^{BC}** of the molecules in the presence of a magnetic field

The difference between the excitation energies and corresponding orbital energy gaps, the exciton binding energy, is investigated based on time-dependent (TD) density functional theory (DFT) for long-chain systems: all-trans polyacetylenes and linear oligoacenes. The optimized geometries of these systems indicate that bond length alternations significantly depend on long-range exchange interactions. In TDDFT formalism, the exciton binding energy comes from the two-electron interactions between occupied and unoccupied orbitals through the Coulomb-exchange-correlation integral kernels. TDDFT calculations show that the exciton binding energy is significant when long-range exchange interactions are involved. Spin-flip (SF) TDDFT calculations are then carried out to clarify double-excitation effects in these excitation energies. The calculated SF-TDDFT results indicate that double-excitation effects significantly contribute to the excitations of long-chain systems. The discrepancies between the vertical ionization potential minus electron affinity (IP–EA) values and the HOMO–LUMO excitation energies are also evaluated for the infinitely long polyacetylene and oligoacene using the least-square fits to estimate the exciton binding energy of infinitely long systems. It is found that long-range exchange interactions are required to give the exciton binding energy of the infinitely long systems. Consequently, it is concluded that long-range exchange interactions neglected in many DFT calculations play a crucial role in the exciton binding energies of long-chain systems, while double-excitation correlation effects are also significant to hold the energy balance of the excitations. © 2016 Wiley Periodicals, Inc.

Exciton binding energy comes from two electron interactions between occupied and unoccupied orbitals through Coulomb-exchange-correlation integral kernels *f*_{Cxc}, in which long-range exchange interactions play.

Theoretical investigations predict that the singlet states of ylide-substituted remote carbenes are significantly stable and comparable to those of experimentally known NHCs. They are also found to be strongly σ-donating in nature as evident from an evaluation of the carbonyl stretching frequencies (*ν*_{CO}) of their complexes with the [Rh(CO)_{2}Cl] fragment. NICS and QTAIM based bond magnetizability calculations indicate the presence of cyclic electron delocalization in majority of the molecules. © 2016 Wiley Periodicals, Inc.

Quantum chemical calculations show that ylide substituted remote *N*-heterocyclic carbenes have significantly enhanced singlet-triplet gaps. Many of the molecules considered in this study are predicted to be stable enough for isolation.

Transcription factors (TFs) are the proteins involved in the transcription process, ensuring the correct expression of specific genes. Numerous diseases arise from the dysfunction of specific TFs. In fact, over 30 TFs have been identified as therapeutic targets of about 9% of the approved drugs. In this study, we created a structural database of small molecule-transcription factor (SM-TF) complexes, available online at http://zoulab.dalton.missouri.edu/SM-TF. The 3D structures of the co-bound small molecule and the corresponding binding sites on TFs are provided in the database, serving as a valuable resource to assist structure-based drug design related to TFs. Currently, the SM-TF database contains 934 entries covering 176 TFs from a variety of species. The database is further classified into several subsets by species and organisms. The entries in the SM-TF database are linked to the UniProt database and other sequence-based TF databases. Furthermore, the druggable TFs from human and the corresponding approved drugs are linked to the DrugBank. © 2016 Wiley Periodicals, Inc.

SM-TF is a structural database of small molecule-transcription factor complexes, which consists of 936 entries covering 176 TFs from a variety of species. The database is further classified into subsets by species and organisms. The entries in the SM-TF database are linked to other databases such as UniProt and DrugBank for detailed biological information. The database serves as a valuable resource to assist structure-based drug design targeting TFs and is freely available at http://zoulab.dalton.missouri.edu/SM-TF.

A new direct summation method, named as polyhedron method, is proposed to calculate Madelung energy. This method calculates sums of electrostatic interactions over sets of neutral polyhedron unit pairs rather than conventional ion pairs; this gives Madelung constant in a matrix. With robustly rapid convergence, polyhedron method is generally applicable for complex compounds containing multiple polyhedral building-blocks and numerical polyhedral connection modes. The matrical analysis suggests face-sharing between octahedral pairs and edge-sharing between tetrahedral pairs can be electrostatically stable, against Pauling's third rule. Further, the matrical calculation of Madelung energies offers a unique advantage to evaluate enormous configurations of cation distributions in a given lattice in a high-throughput manner. That is applicable to study solid solution composites, polymorphism, and defect structures, including but not limited to intermediate phase of delithiated cathode compounds, charge order or antisite defects, and extensively magnetic order. © 2016 Wiley Periodicals, Inc.

A new method is proposed to study electrostatic interactions among polyhedral building-blocks in complex crystals within point charge approximation. By counting group interaction between neutral polyhedron unit pairs, the Madelung constant is obtained in matrix form, revealing the geometric correlations among interstitial sites in lattice. Distinct cationic distributions can be classified according to Madelung energies by high-throughput matrix algebra.

An investigation of the energetics of small lithium clusters doped either with a hydrogen or with a fluorine atom as a function of the number of lithium atoms using fixed-node diffusion quantum Monte Carlo (DMC) simulation is reported. It is found that the binding energy (BE) for the doped clusters increases in absolute values leading to a more stable system than for the pure ones in excellent agreement with available experimental measurements. The BE increases for pure, remains almost constant for hydrogenated, and decreases rapidly toward the bulk lithium for the fluoride as a function of the number of lithium atoms in the clusters. The BE, dissociation energy as well as the second difference in energy display a pronounced odd–even oscillation with the number of lithium atoms. The electron correlation inverts the odd–even oscillation pattern for the doped in comparison with the pure clusters and has an impact of 29%–83% to the BE being higher in the pure cluster followed by the hydrogenated and then by the fluoride. The dissociation energy and the second difference in energy indicate that the doped cluster Li_{3}H is the most stable whereas among the pure ones the more stable are Li_{2}, Li_{4}, and Li_{6}. The electron correlation energy is crucial for the stabilization of Li_{3}H. © 2016 Wiley Periodicals, Inc.

Lithium clusters attract great attention due to their simplicity and potential to technological applications. Although considered simple they are still a challenge for theorists and experimentalists. A major issue in this respect is the energetics and stability of these systems and their dependence on the charge distribution in the cluster formation. This article uses accurate methods to date to discuss the energetics and electron correlation effects in small doped lithium clusters with hydrogen and fluorine atoms.

The MReaDy program was designed for studying Multiprocess Reactive Dynamic systems, that is, complex chemical systems involving different and concurrent reactions. It builds a global potential energy surface integrating a variety of potential energy surfaces, each one of them representing an elementary reaction expected to play a role in the chemical process. For each elementary reaction, energy continuity problems may happen in the transition between potential energy surfaces due to differences in the functional form for each of the fragments, especially if built by different authors. A *N*-dimensional switch function is introduced in MReaDy in order to overcome such a problem. As an example, results of a collision trajectory calculation for H_{2} + OH H_{3}O are presented, showing smooth transition in the potential energy, leading to conservation in the total energy. Calculations for a hydrogen combustion system from 1000 K up to 4000 K shows a variation of 0.012% when compared to the total energy of the system. © 2016 Wiley Periodicals, Inc.

Energy continuity problems may happen in the transition between potential energy surfaces due to the differences in the functional form for each of the fragments. When combining two or more one-dimensional switch function into a *N*-dimensional switch function, the harmonic mean warrants the prevalence of the shorter distance. Up to four-dimensional switch functions are introduced in the MReaDy program in order to overcome such problems.

A zone-folding approach is applied to estimate the thermodynamic properties of V_{2}O_{5}-based nanotubes. The results obtained are compared with those from the direct calculations. It is shown that the zone-folding approximation allows an accurate estimation of nanotube thermodynamic properties and gives a gain in computation time compared to their direct calculations. Both approaches show that temperature effects do not change the relative stability of V_{2}O_{5} free layers and nanotubes derived from the α- and γ-phase. The internal energy thermal contributions into the strain energy of nanotubes are small and can be ignored. © 2016 Wiley Periodicals, Inc.

This article presents results of DFT calculation of the thermodynamic properties of V2O5-based single wall nanotubes using the zone-folding approach and compare them with those from the direct calculations. Zone-folding approach allows an accurate estimation of thermodynamic properties of nanotubes with sufficiently large diameters and provides a gain in computation time compared to their direct calculation.

Density Functional Theory (DFT)-based Global reactivity descriptor calculations have emerged as powerful tools for studying the reactivity, selectivity, and stability of chemical and biological systems. A Python-based module, PyGlobal has been developed for systematically parsing a typical Gaussian outfile and extracting the relevant energies of the HOMO and LUMO. Corresponding global reactivity descriptors are further calculated and the data is saved into a spreadsheet compatible with applications like Microsoft Excel and LibreOffice. The efficiency of the module has been accounted by measuring the time interval for randomly selected Gaussian outfiles for 1000 molecules. © 2016 Wiley Periodicals, Inc.

A Python-based toolkit designed for the purpose of automating the calculation of Global reactivity descriptors such as electronegativity, global hardness, global softness, and chemical potential from the energy values of the highest occupied and lowest occupied molecular orbitals of a molecular system

On page 1388 (DOI: 10.1002/jcc.24348) Muhammad A. Hagras and Alexei A. Stuchebrukhov present the program Electron Tunneling in Proteins to streamline computations and aid in the visualization of electron tunneling in proteins. The top half of the cover shows volume, streamlines, and oriented 3D vectors visualizations of the tunneling currents of the heme *b*_{L}heme *b*_{H} redox system in the ON conformation of the Phe90 residue. The bottom half of the cover shows volume, streamlines, and oriented 3D vectors visualizations of the same tunneling currents when the Phe90 residue is in the OFF conformation. Different representations are colored based on the tunneling flux density from highest (blue) to lowest (red).

The Electron Tunneling in Proteins procedure, presented by Muhammad A. Hagras and Alexei A. Stuchebrukhov on page 1388 (DOI: 10.1002/jcc.24348), incorporates protein pruning, quantum mechanical calculations, bi-orthogonalization, tunneling current calculations, and visualizations. The cover shows the electron tunneling flux through a dividing surface in the heme *b*_{L}hem *b*_{H} redox system at two different Phe90 conformations (ON_{LH} and OFF_{LH}). The flux plot in the lower half shows the edge-to-edge tunneling flux at the two conformations plotted as log_{10} of the flux, adjusted by multipling by 10^{3}, against the normalized coordinate.

Charge transport properties of materials composed of small organic molecules are important for numerous optoelectronic applications. A material's ability to transport charges is considerably influenced by the charge reorganization energies of the composing molecules. Hence, predictions about charge-transport properties of organic materials deserve reliable statements about these charge reorganization energies. However, using density functional theory which is mostly used for the predictions, the computed reorganization energies depend strongly on the chosen functional. To gain insight, a benchmark of various density functionals for the accurate calculation of charge reorganization energies is presented. A correlation between the charge reorganization energies and the ionization potentials is found which suggests applying IP-tuning to obtain reliable values for charge reorganization energies. According to benchmark investigations with IP-EOM-CCSD single-point calculations, the tuned functionals provide indeed more reliable charge reorganization energies. Among the standard functionals, ωB97X-D and SOGGA11X yield accurate charge reorganization energies in comparison with IP-EOM-CCSD values. © 2016 Wiley Periodicals, Inc.

Charge transport in molecular organic semiconductors is important for numerous optoelectronic devices, like organic light-emitting diodes or organic transistors. The efficiency of charge transport is strongly influenced by charge reorganization energies of the semiconducting molecules, which are usually calculated with DFT. A benchmark is presented that evaluates the performance of DFT functionals for computing charge reorganization energies and suggesting IP-tuning in combination with IP-EOM-CCSD calculations to obtain highly accurate charge reorganization energies.

The main-group 6*p* elements did not receive much attention in the development of recent density functionals. In many cases it is still difficult to choose among the modern ones a relevant functional for various applications. Here, we illustrate the case of astatine species (At, *Z* = 85) and we report the first, and quite complete, benchmark study on several properties concerning such species. Insights on geometries, transition energies and thermodynamic properties of a set of 19 astatine species, for which reference experimental or theoretical data has been reported, are obtained with relativistic (two-component) density functional theory calculations. An extensive set of widely used functionals is employed. The hybrid meta-generalized gradient approximation (meta-GGA) PW6B95 functional is overall the best choice. It is worth noting that the range-separated HSE06 functional as well as the old and very popular B3LYP and PBE0 hybrid-GGAs appear to perform quite well too. Moreover, we found that astatine chemistry in solution can accurately be predicted using implicit solvent models, provided that specific parameters are used to build At cavities. © 2016 Wiley Periodicals, Inc.

Two-component density functional theory can be successfully used to predict relevant observables of astatine species, e.g. equilibrium constants. However, recently developed density functionals fail in such applications involving astatine, a main-group element.

The electronic structure and chemical bonding in donor–acceptor complexes formed by group 13 element adamantane and perfluorinated adamantane derivatives EC_{9}R′_{15} (E = B, Al; R′ = H, F) with Lewis bases XR_{3} and XC_{9}H_{15} (X = N, P; R= H, CH_{3}) have been studied using energy decomposition analysis at the BP86/TZ2P level of theory. Larger stability of complexes with perfluorinated adamantane derivatives is mainly due to better electrostatic and orbital interactions. Deformation energies of the fragments and Pauli repulsion are of less importance, with exception for the boron-phosphorus complexes. The MO analysis reveals that LUMO energies of EC_{9}R′_{15} significantly decrease upon fluorination (by 4.7 and 3.6 eV for E = B and Al, respectively) which results in an increase of orbital interaction energies by 27–38 (B) and 15–26 (Al) kcal mol^{−1}. HOMO energies of XR_{3} increase in order PH_{3} < NH_{3} < PMe_{3} < PC_{9}H_{15} < NMe_{3} < NC_{9}H_{15}. For the studied complexes, there is a linear correlation between the dissociation energy of the complex and the energy difference between HOMO of the donor and LUMO of the acceptor. The fluorination of the Lewis acid significantly reduces standard enthalpies of the heterolytic hydrogen splitting H_{2} + D + A = [HD]^{+} + [HA]^{−}. Analysis of several types of the [HD]^{+}···[HA]^{−} ion pair formation in the gas phase reveals that structures with additional H···F interactions are energetically favorable. Taking into account the ion pair formation, hydrogen splitting is predicted to be highly exothermic in case of the perfluorinated derivatives both in the gas phase and in solution. Thus, fluorinated adamantane-based Lewis superacids are attractive synthetic targets for the construction of the donor–acceptor cryptands. © 2016 Wiley Periodicals, Inc.

The electronic structure and chemical bonding in donor–acceptor complexes formed by group 13 element adamantane and perfluorinated adamantane derivatives with Lewis bases have been studied using energy decomposition analysis. There is a linear correlation between the dissociation energy of the complex and the energy difference between HOMO of the donor and LUMO of the acceptor. The fluorination of the Lewis acid significantly reduces standard enthalpies of the heterolytic hydrogen splitting.

The open edge reconstruction of half-saturated (6,0) zigzag carbon nanotube (CNT) was introduced by density functional calculations. The multistep rearrangement was demonstrated as a regioselective process to generate a defective edge with alternating pentagons and heptagons. Not only the thermal stability was found to be enhanced significantly after reconstruction but also the total spin of CNT was proved to be reduced gradually from high-spin septet to close-shell singlet, revealing the critical role of deformed edge on the geometrical and magnetic properties of open-ended CNTs. Kinetically, the initial transformation was confirmed as the rate-determining step with relatively the largest reaction barrier and the following steps can take place spontaneously. © 2016 Wiley Periodicals, Inc.

The open edge reconstruction mechanism of half-saturated zigzag carbon nanotube (CNT) is explored by density functional thoery calculations for the first time. The reconstruction process from a bared zigzag edge to a defective edge with sequential pentagonal-heptagonal pairs is proved as a regioselective stabilization process and the total spin of half-saturated CNT dramatically transforms from high-spin state to close-shell singlet.

This work reports on the comprehensive calculation of the NMR one-bond spin–spin coupling constants (SSCCs) involving carbon and tellurium, ^{1}*J*(^{125}Te,^{13}C), in four representative compounds: Te(CH_{3})_{2}, Te(CF_{3})_{2}, Te(CCH)_{2}, and tellurophene. A high-level computational treatment of ^{1}*J*(^{125}Te,^{13}C) included calculations at the SOPPA level taking into account relativistic effects evaluated at the 4-component RPA and DFT levels of theory, vibrational corrections, and solvent effects. The consistency of different computational approaches including the level of theory of the geometry optimization of tellurium-containing compounds, basis sets, and methods used for obtainig spin–spin coupling values have also been discussed in view of reproducing the experimental values of the tellurium–carbon SSCCs. Relativistic corrections were found to play a major role in the calculation of ^{1}*J*(^{125}Te,^{13}C) reaching as much as almost 50% of the total value of ^{1}*J*(^{125}Te,^{13}C) while relativistic geometrical effects are of minor importance. The vibrational and solvent corrections account for accordingly about 3–6% and 0–4% of the total value. It is shown that taking into account relativistic corrections, vibrational corrections and solvent effects at the DFT level essentially improves the agreement of the non-relativistic theoretical SOPPA results with experiment. © 2016 Wiley Periodicals, Inc.

The paper reports on the comprehensive calculation of the one-bond spin–spin coupling constants involving carbon and tellurium, ^{1}*J*(^{125}Te,^{13}C), in Te(CH_{3})_{2}, Te(CF_{3})_{2}, Te(CCH)_{2}, and tellurophene taking into account relativistic effects evaluated at the 4-component RPA and DFT levels of theory, vibrational corrections, and solvent effects. Relativistic corrections were found to play a major role reaching as much as almost 50% of the total value of ^{1}*J*(^{125}Te,^{13}C).

A method designed to investigate, on a fundamental level, the origin of relative stability of molecular systems using Be^{II} complexes with nitrilotriacetic acid (NTA) and nitrilotri-3-propionic acid (NTPA) is described. It makes use of the primary and molecular fragment energy terms as defined in the IQA/F (Interacting Quantum Atoms/Fragments) framework. An extensive classical-type investigation, focused on single descriptors (bond length, density at critical point, the size of metal ion or coordination ring, interaction energy between Be^{II} and a donor atom, etc.) showed that it is not possible to explain the experimental trend. The proposed methodology is fundamentally different in that it accounts for the total energy contributions coming from all atoms of selected molecular fragments, and monitors changes in defined energy terms (*e.g*., fragment deformation, inter- and intra-fragment interaction) on complex formation. By decomposing combined energy terms we identified the origin of relative stability of Be^{II}(NTA) and Be^{II}(NTPA) complexes. We found that the sum of coordination bonds' strength, as measured by interaction energies between Be^{II} ion and donor atoms, favours Be^{II}(NTA) but the binding energy of Be^{II} ion to the entire ligand correlates well with experimental trend. Surprisingly, the origin of Be^{II}(NTPA) being more stable is due to less severe repulsive interactions with the backbone of NTPA (C and H-atoms). This general purpose protocol can be employed not only to investigate the origin of relative stability of any molecular system (*e.g*., metal complexes) but, in principle, can be used as a predictive tool for, *e.g*., explaining reaction mechanism. © 2016 Wiley Periodicals, Inc.

This methodology accounts for the total energy contributions coming from all atoms of selected molecular fragments. By decomposing changes in, for example, fragment deformation, interfragment and intrafragment interaction energies, the origin of complexes relative stability was identified. Although coordination bonds' strength favors BeNTA, the origin of BeNTPA being more stable was found to be due to less sever repulsive interactions with the backbone of NTPA (C and H-atoms).

We developed a unique integrated software package (called Electron Tunneling in Proteins Program or ETP) which provides an environment with different capabilities such as tunneling current calculation, semi-empirical quantum mechanical calculation, and molecular modeling simulation for calculation and analysis of electron transfer reactions in proteins. ETP program is developed as a cross-platform client-server program in which all the different calculations are conducted at the server side while only the client terminal displays the resulting calculation outputs in the different supported representations. ETP program is integrated with a set of well-known computational software packages including Gaussian, BALLVIEW, Dowser, pKip, and APBS. In addition, ETP program supports various visualization methods for the tunneling calculation results that assist in a more comprehensive understanding of the tunneling process. © 2016 Wiley Periodicals, Inc.

Electron tunneling calculation is an extensive multitier procedure which incorporates protein pruning, quantum mechanical calculation, biorthogonalization and tunneling current calculation, and visualization. We developed the Electron Tunneling in Proteins (ETP) program to automate such a lengthy process in a streamlined fashion and utilizing user-friendly interfaces. ETP program is integrated with different well-established packages and in addition provides different visualization schemes for the calculated tunneling currents which assist to better comprehend the tunneling process.

Fullerene-based molecular heterojunctions such as the [6,6]-pyrrolidine-C_{60} donor–acceptor conjugate containing triphenylamine (TPA) are potential materials for high-efficient dye-sensitized solar cells. In this work, we estimate the rate constants for the photoinduced charge separation and charge recombination processes in TPA-C_{60} using the unrestricted and time-dependent DFT methods. Different schemes are applied to evaluate excited state properties and electron transfer parameters (reorganization energies, electronic couplings, and Gibbs energies). The use of open-shell singlet or triplet states, several density functionals, and continuum solvation models is discussed. Strengths and limitations of the computational approaches are highlighted. The present benchmark study provides an overview of the expected performance of DFT-based methodologies in the description of photoinduced charge transfer reactions in fullerene heterojunctions. © 2016 Wiley Periodicals, Inc.

This work analyzes the photoinduced charge transfer reactions in the molecular heterojunction formed by a TPA-C_{60} donor–acceptor conjugate. Our aim is to assess the performance of DFT-based methodologies for the description of the charge transfer reactions in molecular heterojunctions-based on fullerenes by comparison with the available experimental results.