Showing papers in "Journal of Chemical Theory and Computation in 2010"

g_wham—A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates

Abstract: The Weighted Histogram Analysis Method (WHAM) is a standard technique used to compute potentials of mean force (PMFs) from a set of umbrella sampling simulations. Here, we present a new WHAM implementation, termed g_wham, which is distributed freely with the GROMACS molecular simulation suite. g_wham estimates statistical errors using the technique of bootstrap analysis. Three bootstrap methods are supported: (i) bootstrapping new trajectories based on the umbrella histograms, (ii) bootstrapping of complete histograms, and (iii) Bayesian bootstrapping of complete histograms, that is, bootstrapping via the assignment of random weights to the histograms. Because methods ii and iii consider only complete histograms as independent data points, these methods do not require the accurate calculation of autocorrelation times. We demonstrate that, given sufficient sampling, bootstrapping new trajectories allows for an accurate error estimate. In the presence of long autocorrelations, however, (Bayesian) bootstrapp...

Prediction of Absolute Solvation Free Energies using Molecular Dynamics Free Energy Perturbation and the OPLS Force Field.

Abstract: The accurate prediction of protein−ligand binding free energies is a primary objective in computer-aided drug design. The solvation free energy of a small molecule provides a surrogate to the desolvation of the ligand in the thermodynamic process of protein−ligand binding. Here, we use explicit solvent molecular dynamics free energy perturbation to predict the absolute solvation free energies of a set of 239 small molecules, spanning diverse chemical functional groups commonly found in drugs and drug-like molecules. We also compare the performance of absolute solvation free energies obtained using the OPLS_2005 force field with two other commonly used small molecule force fields—general AMBER force field (GAFF) with AM1-BCC charges and CHARMm-MSI with CHelpG charges. Using the OPLS_2005 force field, we obtain high correlation with experimental solvation free energies (R2 = 0.94) and low average unsigned errors for a majority of the functional groups compared to AM1-BCC/GAFF or CHelpG/CHARMm-MSI. However, ...

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries

Abstract: Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Implementation of the CHARMM force field in GROMACS : Analysis of protein stability effects from correction maps, virtual interaction sites, and water models

Abstract: CHARMM27 is a widespread and popular force field for biomolecular simulation, and several recent algorithms such as implicit solvent models have been developed specifically for it. We have here implemented the CHARMM force field and all necessary extended functional forms in the GROMACS molecular simulation package, to make CHARMM-specific features available and to test them in combination with techniques for extended time steps, to make all major force fields available for comparison studies in GROMACS, and to test various solvent model optimizations, in particular the effect of Lennard-Jones interactions on hydrogens. The implementation has full support both for CHARMM-specific features such as multiple potentials over the same dihedral angle and the grid-based energy correction map on the ϕ, ψ protein backbone dihedrals, as well as all GROMACS features such as virtual hydrogen interaction sites that enable 5 fs time steps. The medium-to-long time effects of both the correction maps and virtual sites have been tested by performing a series of 100 ns simulations using different models for water representation, including comparisons between CHARMM and traditional TIP3P. Including the correction maps improves sampling of near native-state conformations in our systems, and to some extent it is even able to refine distorted protein conformations. Finally, we show that this accuracy is largely maintained with a new implicit solvent implementation that works with virtual interaction sites, which enables performance in excess of 250 ns/day for a 900-atom protein on a quad-core desktop computer.

Auxiliary Density Matrix Methods for Hartree-Fock Exchange Calculations.

Abstract: The calculation of Hartree-Fock exchange (HFX) is computationally demanding for large systems described with high-quality basis sets. In this work, we show that excellent performance and good accuracy can nevertheless be obtained if an auxiliary density matrix is employed for the HFX calculation. Several schemes to derive an auxiliary density matrix from a high-quality density matrix are discussed. Key to the accuracy of the auxiliary density matrix methods (ADMM) is the use of a correction based on standard generalized gradient approximations for HFX. ADMM integrates seamlessly in existing HFX codes and, in particular, can be employed in linear scaling implementations. Demonstrating the performance of the method, the effect of HFX on the structure of liquid water is investigated in detail using Born-Oppenheimer molecular dynamics simulations (300 ps) of a system of 64 molecules. Representative for large systems are calculations on a solvated protein (Rubredoxin), for which ADMM outperforms the corresponding standard HFX implementation by approximately a factor 20.

A General Database for Main Group Thermochemistry, Kinetics, and Noncovalent Interactions − Assessment of Common and Reparameterized (meta-)GGA Density Functionals

Abstract: We present a quantum chemistry benchmark database for general main group thermochemistry, kinetics, and noncovalent interactions (GMTKN24). It is an unprecedented compilation of 24 different, chemically relevant subsets that either are taken from already existing databases or are presented here for the first time. The complete set involves a total of 1.049 atomic and molecular single point calculations and comprises 731 data points (relative chemical energies) based on accurate theoretical or experimental reference values. The usefulness of the GMTKN24 database is shown by applying common density functionals on the (meta-)generalized gradient approximation (GGA), hybrid-GGA, and double-hybrid-GGA levels to it, including an empirical London dispersion correction. Furthermore, we refitted the functional parameters of four (meta-)GGA functionals based on a fit set containing 143 systems, comprising seven chemically different problems. Validation against the GMTKN24 and the molecular structure (bond lengths) ...

Simulating Monovalent and Divalent Ions in Aqueous Solution Using a Drude Polarizable Force Field

Abstract: An accurate representation of ion solvation in aqueous solution is critical for meaningful computer simulations of a broad range of physical and biological processes. Polarizable models based on classical Drude oscillators are introduced and parametrized for a large set of monatomic ions including cations of the alkali metals (Li+, Na+, K+, Rb+, and Cs+) and alkaline earth elements (Mg2+, Ca2+, Sr2+, and Ba2+) along with Zn2+ and halide anions (F−, Cl−, Br−, and I−). The models are parametrized, in conjunction with the polarizable SWM4-NDP water model [Lamoureux et al. Chem. Phys. Lett. 2006, 418, 245], to be consistent with a wide assortment of experimentally measured aqueous bulk thermodynamic properties and the energetics of small ion−water clusters. Structural and dynamic properties of the resulting ion models in aqueous solutions at infinite dilution are presented.

On the Performances of the M06 Family of Density Functionals for Electronic Excitation Energies

Abstract: We assessed the accuracy of the four members of the M06 family of functionals (M06-L, M06, M06-2X, and M06-HF) for the prediction of electronic excitation energies of main-group compounds by time-dependent density functional theory. This is accomplished by comparing the predictions both to high-level theoretical benchmark calculations and some experimental data for gas-phase excitation energies of small molecules and to experimental data for midsize and large chromogens in liquid-phase solutions. The latter comparisons are carried out using implicit solvation models to include the electrostatic effects of solvation. We find that M06-L is one of the most accurate local functionals for evaluating electronic excitation energies, that M06-2X outperforms BHHLYP, and that M06-HF outperforms HF, although in each case, the compared functionals have the same or a similar amount of Hartree-Fock exchange. For the majority of investigated excited states, M06 emerges as the most accurate functional among the four tested, and it provides an accuracy similar to the best of the other global hybrids such as B3LYP, B98, and PBE0. For 190 valence excited states, 20 Rydberg states, and 16 charge transfer states, we try to provide an overall assessment by comparing the quality of the predictions to those of time-dependent Hartree-Fock theory and nine other density functionals. For the valence excited states, M06 yields a mean absolute deviation (MAD) of 0.23 eV, whereas B3LYP, B98, and PBE0 have MADs in the range 0.19-0.22 eV. Of the functionals tested, M05-2X, M06-2X, and BMK are found to perform best for Rydberg states, and M06-HF performs best for charge transfer states, but no single functional performs satisfactorily for all three kinds of excitation. The performance of functionals with no Hartree-Fock exchange is of great practical interest because of their high computational efficiency, and we find that M06-L predicts more accurate excitation energies than other such functionals.

Exploring Multidimensional Free Energy Landscapes Using Time-Dependent Biases on Collective Variables

Abstract: A new implementation of the adaptive biasing force (ABF) method is described. This implementation supports a wide range of collective variables and can be applied to the computation of multidimensional energy profiles. It is provided to the community as part of a code that implements several analogous methods, including metadynamics. ABF and metadynamics have not previously been tested side by side on identical systems. Here, numerical tests are carried out on processes including conformational changes in model peptides and translocation of a halide ion across a lipid membrane through a peptide nanotube. On the basis of these examples, we discuss similarities and differences between the ABF and metadynamics schemes. Both approaches provide enhanced sampling and free energy profiles in quantitative agreement with each other in different applications. The method of choice depends on the dimension of the reaction coordinate space, the height of the barriers, and the relaxation times of degrees of freedom in the orthogonal space, which are not explicitly described by the chosen collective variables.

Structural Survey of Zinc Containing Proteins and the Development of the Zinc AMBER Force Field (ZAFF)

Abstract: Currently the Protein Data Bank (PDB) contains over 25 000 structures that contain a metal ion including Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Pd, Ag, Cd, Ir, Pt, Au, and Hg. In general, carrying out classical molecular dynamics (MD) simulations of metalloproteins is a convoluted and time-consuming process. Herein, we describe MCPB (Metal Center Parameter Builder), which allows one to conveniently and rapidly incorporate metal ions using the bonded plus electrostatics model (Hoops et al. J. Am. Chem. Soc. 1991, 113, 8262−8270) into the AMBER force field (FF). MCPB was used to develop a zinc FF, ZAFF, which is compatible with the existing AMBER FFs. The PDB was mined for all Zn-containing structures with most being tetrahedrally bound. The most abundant primary shell ligand combinations were extracted, and FFs were created. These include Zn bound to CCCC, CCCH, CCHH, CHHH, HHHH, HHHO, HHOO, HOOO, HHHD, and HHDD (O = water and the remaining are 1-letter amino acid codes). Bond and angle force consta...

Chemically Meaningful Atomic Charges That Reproduce the Electrostatic Potential in Periodic and Nonperiodic Materials.

Abstract: Net atomic charges (NACs) can be used both to understand the chemical states of atoms in a material as well as to represent the electrostatic potential, V, of the material outside its electron distribution. However, many existing definitions of NACs have limitations that prevent them from adequately fulfilling this dual purpose. Some charge methods are not applicable to periodic materials or are inaccurate for systems containing buried atoms, while others work for both periodic and nonperiodic materials containing buried atoms but give NACS that do not accurately reproduce V. We present a new approach, density derived electrostatic and chemical (DDEC) charges, that overcomes these limitations by simultaneously optimizing the NACs to be chemically meaningful and to reproduce V outside the electron distribution. This atoms-in-molecule method partitions the total electron density among atoms and uses a distributed multipole expansion to formally reproduce V exactly outside the electron distribution. We compare different methods for computing NACs for a broad range of materials that are periodic in zero, one, two, and three dimensions. The DDEC method consistently performs well for systems with and without buried atoms, including molecules, nonporous solids, solid surfaces, and porous solids like metal organic frameworks.

Performance of Molecular Mechanics Force Fields for RNA Simulations: Stability of UUCG and GNRA Hairpins

Abstract: The RNA hairpin loops represent important RNA topologies with indispensable biological functions in RNA folding and tertiary interactions. 5′-UNCG-3′ and 5′-GNRA-3′ RNA tetraloops are the most important classes of RNA hairpin loops. Both tetraloops are highly structured with characteristic signature three-dimensional features and are recurrently seen in functional RNAs and ribonucleoprotein particles. Explicit solvent molecular dynamics (MD) simulation is a computational technique which can efficiently complement the experimental data and provide unique structural dynamics information on the atomic scale. Nevertheless, the outcome of simulations is often compromised by imperfections in the parametrization of simplified pairwise additive empirical potentials referred to also as force fields. We have pointed out in several recent studies that a force field description of single-stranded hairpin segments of nucleic acids may be particularly challenging for the force fields. In this paper, we report a critica...

Integration Grid Errors for Meta-GGA-Predicted Reaction Energies: Origin of Grid Errors for the M06 Suite of Functionals

Abstract: We have assessed integration grid errors arising from the use of popular DFT quadrature schemes for a set of 34 organic reaction energies. The focus is primarily on M05-2X and the M06 suite of functionals (M06-L, M06, M06-2X, and M06-HF). M05-2X, M06, and M06-2X outperform popular older DFT functionals for the reaction energies studied and offer accuracies comparable to results from perturbative hybrid DFT functionals. However, these new functionals are more sensitive to the choice of quadrature grid than previous generations of DFT functionals. Errors in predicted reaction energies arising from the use of the popular SG-1 integration grid, which is the default in the Q-Chem package, are significant. In particular, M06-HF reaction energies computed with the SG-1 grid exhibit errors ranging from −6.7 to 3.2 kcal mol−1, relative to results computed with a very fine integration grid. This grid sensitivity is not a general problem for meta-generalized gradient approximation functionals, but is instead due to ...

Excited States in Solution through Polarizable Embedding

Abstract: We present theory and implementation of an advanced quantum mechanics/molecular mechanics (QM/MM) approach using a fully self-consistent polarizable embedding (PE) scheme. It is a polarizable layered model designed for effective yet accurate inclusion of an anisotropic medium in a quantum mechanical calculation. The polarizable embedding potential is described by an atomistic representation including terms up to localized octupoles and anisotropic polarizabilities. It is generally applicable to any quantum chemical description but is here implemented for the case of Kohn−Sham density functional theory which we denote the PE-DFT method. It has been implemented in combination with time-dependent quantum mechanical linear and nonlinear response techniques, thus allowing for assessment of electronic excitation processes and dynamic ground- and excited-state molecular properties using a nonequilibrium formulation of the environmental response. In our formulation of polarizable embedding we explicitly take into...

On the validation of molecular dynamics simulations of saturated and cis-monounsaturated phosphatidylcholine lipid bilayers: A comparison with experiment

Abstract: Molecular dynamics simulations of fully hydrated pure bilayers of four widely studied phospholipids, 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) using a recent revision of the GROMOS96 force field are reported. It is shown that the force field reproduces the structure and the hydration of bilayers formed by each of the four lipids with high accuracy. Specifically, the solvation and the orientation of the dipole of the phosphocholine headgroup and of the ester carbonyls show that the structure of the primary hydration shell in the simulations closely matches experimental findings. This work highlights the need to reproduce a broad range of properties beyond the area per lipid, which is poorly defined experimentally, and to consider the effect of system size and sampling times well beyond those commonly used.

Harmonic and Anharmonic Vibrational Frequency Calculations with the Double-Hybrid B2PLYP Method: Analytic Second Derivatives and Benchmark Studies

Abstract: This work aims to provide reliable benchmark data on the accuracy of harmonic and anharmonic vibrational frequencies computed with the B2PLYP double-hybrid density functional method. The exchange-correlation contributions required for the B2PLYP analytical second derivatives are presented here, which allow for the effective calculation of harmonic frequency as well as cubic and semidiagonal quartic force fields. The latter, in turn, are necessary to compute the anharmonic vibrational frequencies with the perturbative approach (VPT2). The quality of harmonic vibrational frequencies computed in conjunction with basis sets of double- to quadruple-ζ quality has been checked against reference data from the F38 benchmark set. Then, for an additional set of small closed- and open-shell systems, both harmonic frequencies and anharmonic contributions computed at the B2PLYP/N07D and the B2PLYP/aug-cc-pVTZ levels have been compared to their CCSD(T) counterparts. Moreover, for selected medium-size molecules (furan, pyrrole, thiophene, uracil, anisole, phenol, and pyridine), anharmonic frequencies have been compared to well established experimental results. Such benchmark studies have shown that the B2PLYP/N07D model provides good quality harmonic frequencies and describes correctly anharmonic contributions, the latter being of similar accuracy to their B3LYP/N07D counterparts, but obtained at significantly larger computational cost. Additionally, increased accuracy can be obtained by adopting hybrid models where the B2PLYP/N07D anharmonic contributions are combined with harmonic frequencies computed with more accurate quantum mechanical (QM) approaches or by B2PLYP with larger basis sets. This work confirmed also that most of the recently developed density functionals are significantly less suited for vibrational computations, while the B2PLYP method can be recommended for spectroscopic studies where a good accuracy of vibrational properties is required.

A Transferable H-Bonding Correction for Semiempirical Quantum-Chemical Methods.

Abstract: Semiempirical methods could offer a feasible compromise between ab initio and empirical approaches for the calculation of large molecules with biological relevance. A key problem for attempts in this direction is the rather bad performance of current semiempirical methods for noncovalent interactions, especially hydrogen-bonding. On the basis of the recently introduced PM6-DH method, which includes empirical corrections for dispersion (D) and hydrogen-bond (H) interactions, we have developed an improved and transferable H-bonding correction for semiempirical quantum chemical methods. The performance of the improved correction is evaluated for PM6, AM1, OM3, and SCC-DFTB (enhanced by standard empirical dispersion corrections) with several test sets for noncovalent interactions and is shown to reach the quality of current DFT-D approaches for these types of problems.

General Approach to Compute Vibrationally Resolved One-Photon Electronic Spectra

Abstract: An effective time-independent approach to compute vibrationally resolved optical spectra from first principles is generalized toward the computation of one-photon electronic spectra induced by eith...

Enhanced modeling via network theory: Adaptive sampling of Markov state models.

Abstract: Computer simulations can complement experiments by providing insight into molecular kinetics with atomic resolution. Unfortunately, even the most powerful supercomputers can only simulate small systems for short time scales, leaving modeling of most biologically relevant systems and time scales intractable. In this work, however, we show that molecular simulations driven by adaptive sampling of networks called Markov State Models (MSMs) can yield tremendous time and resource savings, allowing previously intractable calculations to be performed on a routine basis on existing hardware. We also introduce a distance metric (based on the relative entropy) for comparing MSMs. We primarily employ this metric to judge the convergence of various sampling schemes but it could also be employed to assess the effects of perturbations to a system (e.g., determining how changing the temperature or making a mutation changes a system’s dynamics).

Permutationally Invariant Polynomial Basis for Molecular Energy Surface Fitting via Monomial Symmetrization

Abstract: We describe a procedure to develop a fitting basis for molecular potential energy surfaces (PESs) that is invariant with respect to permutation of like atoms. The method is based on a straightforward symmetrization of a primitive monomial basis and illustrated for several classes of molecules. A numerically efficient method to evaluate the resulting expression for the PES is also described. The fitting basis is used to obtain a new PES for H3O(+) based on roughly 62 000 ab initio energies.

Three-Dimensional Molecular Theory of Solvation Coupled with Molecular Dynamics in Amber

Abstract: We present the three-dimensional molecular theory of solvation (also known as 3D-RISM) coupled with molecular dynamics (MD) simulation by contracting solvent degrees of freedom, accelerated by extrapolating solvent-induced forces and applying them in large multiple time steps (up to 20 fs) to enable simulation of large biomolecules. The method has been implemented in the Amber molecular modeling package and is illustrated here on alanine-dipeptide and protein-G.

Third-Generation Hydrogen-Bonding Corrections for Semiempirical QM Methods and Force Fields

Abstract: Computational modeling of biological systems is a rapidly evolving field that calls for methods that are able to allow for extensive sampling with systems consisting of thousands of atoms. Semiempirical quantum chemical (SE) methods are a promising tool to aid with this, but the rather bad performance of standard SE methods for noncovalent interactions is clearly a limiting factor. Enhancing SE methods with empirical corrections for dispersion and hydrogen-bonding interactions was found to be a big improvement, but for the hydrogen-bonding corrections the drawback of breaking down in the case of substantial changes to the hydrogen bond, e.g., proton transfer, posed a serious limitation for its general applicability. This work presents a further improved hydrogen-bonding correction that can be generally included in parameter fitting procedures, as it does not suffer from the conceptual flaws of previous approaches: hydrogen bonds are now treated as an interaction term between electronegative acceptor and d...

Efficient Structure Optimization with Second-Order Many-Body Perturbation Theory: The RIJCOSX-MP2 Method.

Abstract: Efficient energy calculations and structure optimizations employing second-order Moller−Plesset perturbation theory (MP2) are presented. The application of the RIJCOSX approximation, which involves different approximations for the formation of the Coulomb- and exchange-type matrices, to MP2 theory is demonstrated. The RIJCOSX approximation incorporates the ‘resolution of the identity’ approximation in terms of a Split-RI-J variant for the evaluation of the Coulomb matrices and a seminumeric exchange treatment via the ‘chain-of-spheres’ algorithm for the formation of the exchange-type matrices. Beside the derivation of the working equations, the RIJCOSX-MP2 method is benchmarked against the original MP2 and the already highly efficient RI-MP2 method. Energies as well as gradients are computed employing various basis sets and are compared to the conventional MP2 results concerning accuracy and total wall clock times. Speedups of typically a factor of 5−7 in comparison to MP2 can be obeserved for the largest...

How Can Hydrophobic Association Be Enthalpy Driven

Abstract: Hydrophobic association is often recognized as being driven by favorable entropic contributions. Here, using explicit solvent molecular dynamics simulations we investigate binding in a model hydrophobic receptor−ligand system which appears, instead, to be driven by enthalpy and opposed by entropy. We use the temperature dependence of the potential of mean force to analyze the thermodynamic contributions along the association coordinate. Relating such contributions to the ongoing changes in system hydration allows us to demonstrate that the overall binding thermodynamics is determined by the expulsion of disorganized water from the receptor cavity. Our model study sheds light on the solvent-induced driving forces for receptor−ligand association of general, transferable relevance for biological systems with poorly hydrated binding sites.

Comparative Study of Selected Wave Function and Density Functional Methods for Noncovalent Interaction Energy Calculations Using the Extended S22 Data Set.

Abstract: In this paper, an extension of the S22 data set of Jurecka et al. (Jurecka, P.; Sponer, J.; Cerný, J.; Hobza, P. Phys. Chem. Chem. Phys. 2006, 8, 1985.), the data set of benchmark CCSD(T)/CBS interaction energies of twenty-two noncovalent complexes in equilibrium geometries, is presented. The S22 data set has been extended by including the stretched (one shortened and three elongated) complex geometries of the S22 data set along the main noncovalent interaction coordinate. The goal of this work is to assess the accuracy of the popular wave function methods (MP2-, MP3- and, CCSD-based) and density functional methods (with and without empirical correction for the dispersion energy) for noncovalent complexes based on a statistical evaluation not only in equilibrium, but also in nonequilibrium geometries. The results obtained in this work provide information on whether an accurate and balanced description of the different interaction types and complex geometry distortions can be expected from the tested metho...

Free Energy Perturbation Hamiltonian Replica-Exchange Molecular Dynamics (FEP/H-REMD) for Absolute Ligand Binding Free Energy Calculations

Abstract: Free Energy Perturbation with Replica Exchange Molecular Dynamics (FEP/REMD) offers a powerful strategy to improve the convergence of free energy computations. In particular, it has been shown previously that a FEP/REMD scheme allowing random moves within an extended replica ensemble of thermodynamic coupling parameters “λ” can improve the statistical convergence in calculations of absolute binding free energy of ligands to proteins [J. Chem. Theory Comput. 2009, 5, 2583]. In the present study, FEP/REMD is extended and combined with an accelerated MD simulations method based on Hamiltonian replica-exchange MD (H-REMD) to overcome the additional problems arising from the existence of kinetically trapped conformations within the protein receptor. In the combined strategy, each system with a given thermodynamic coupling factor λ in the extended ensemble is further coupled with a set of replicas evolving on a biased energy surface with boosting potentials used to accelerate the interconversion among different...

Colored-Noise Thermostats à la Carte

Abstract: Recently, we have shown how a colored-noise Langevin equation can be used in the context of molecular dynamics as a tool to obtain dynamical trajectories whose properties are tailored to display desired sampling features. In the present paper, after having reviewed some analytical results for the stochastic differential equations forming the basis of our approach, we describe in detail the implementation of the generalized Langevin equation thermostat and the fitting procedure used to obtain optimal parameters. We also discuss the simulation of nuclear quantum effects and demonstrate that by carefully choosing parameters one can successfully model strongly anharmonic solids such as neon. For the readers convenience, a library of thermostat parameters and some demonstrative code can be downloaded from an online repository. © 2010 American Chemical Society.

Electronic Transition Energies: A Study of the Performance of a Large Range of Single Reference Density Functional and Wave Function Methods on Valence and Rydberg States Compared to Experiment.

Abstract: This work reports a comparison among wave function and DFT single reference methods for vertical electronic transition energy calculations toward singlet states, valence and Rydberg in nature. A series of 11 small organic molecules are used as test cases, where accurate experimental data in gas phase are available. We compared CIS, RPA, CIS(D), EOM-CCSD, and 28 multipurpose density functionals of the type LSDA, GGA, M-GGA, H-GGA, HM-GGA and with separated short and long-range exchange. The list of functionals is obviously not complete, but it spans more than 20 years of DFT development and includes functionals which are commonly used in the computation of a variety of molecular properties. Large differences in the results were found between the various functionals. The aim of this work is therefore to shed some light on the performance of the plethora of functionals available and compare them with some traditional wave function based methods on a molecular property of large interest as the transition energy.

Optoelectronic and Excitonic Properties of Oligoacenes: Substantial Improvements from Range-Separated Time-Dependent Density Functional Theory

Abstract: The optoelectronic and excitonic properties in a series of linear acenes (naphthalene up to heptacene) are investigated using range-separated methods within time-dependent density functional theory (TDDFT). In these rather simple systems, it is well-known that TDDFT methods using conventional hybrid functionals surprisingly fail in describing the low-lying L(a) and L(b) valence states, resulting in large, growing errors for the L(a) state and an incorrect energetic ordering as a function of molecular size. In this work, we demonstrate that the range-separated formalism largely eliminates both of these errors and also provides a consistent description of excitonic properties in these systems. We further demonstrate that reoptimizing the percentage of Hartree-Fock exchange in conventional hybrids to match wave function-based benchmark calculations still yields serious errors, and a full 100% Hartree-Fock range separation is essential for simultaneously describing both of the L(a) and L(b) transitions. From an analysis of electron-hole transition density matrices, we finally show that conventional hybrid functionals over-delocalize excitons and underestimate quasiparticle energy gaps in the acene systems. The results of our present study emphasize the importance of both a range-separated and asymptotically correct contribution of exchange in TDDFT for investigating optoelectronic and excitonic properties, even for these simple valence excitations.

Assessment of Functionals for TD-DFT Calculations of Singlet-Triplet Transitions.

Abstract: The calculation of transition energies for electronically excited states remains a challenge in quantum chemistry, for which time-dependent density functional theory (TD-DFT) is often viewed as a balanced (computational effort/obtained accuracy) technique. In this study, we benchmark 34 DFT functionals in the specific framework of TD-DFT calculations for singlet-triplet transitions. The results are compared to accurate wave function data reported for the same set of 63 excited-states, and it turns out that, within the selected TD-DFT framework, BMK and M06-2X emerge as the most efficient hybrids. This investigation clearly illustrates that the conclusions drawn for singlet excited states do not necessarily hold for triplet states, even for similar molecular structures.