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Showing papers in "Journal of Computational Chemistry in 2008"


Journal ArticleDOI
TL;DR: The CHARMM-GUI as mentioned in this paper is a web-based graphical user interface to generate various input files and molecular systems to facilitate and standardize the usage of common and advanced simulation techniques in CHARMM.
Abstract: CHARMM is an academic research program used widely for macromolecular mechanics and dynamics with versatile analysis and manipulation tools of atomic coordinates and dynamics trajectories. CHARMM-GUI, http://www.charmm-gui.org, has been developed to provide a web-based graphical user interface to generate various input files and molecular systems to facilitate and standardize the usage of common and advanced simulation techniques in CHARMM. The web environment provides an ideal platform to build and validate a molecular model system in an interactive fashion such that, if a problem is found through visual inspection, one can go back to the previous setup and regenerate the whole system again. In this article, we describe the currently available functional modules of CHARMM-GUI Input Generator that form a basis for the advanced simulation techniques. Future directions of the CHARMM-GUI development project are also discussed briefly together with other features in the CHARMM-GUI website, such as Archive and Movie Gallery.

4,525 citations


Journal ArticleDOI
TL;DR: The cclib platform as discussed by the authors is a platform for the development of package-independent computational chemistry algorithms, which can automatically detect, parse, and convert the extracted information into a standard internal representation.
Abstract: There are now a wide variety of packages for electronic structure calculations, each of which differs in the algorithms implemented and the output format. Many computational chemistry algorithms are only available to users of a particular package despite being generally applicable to the results of calculations by any package. Here we present cclib, a platform for the development of package-independent computational chemistry algorithms. Files from several versions of multiple electronic structure packages are automatically detected, parsed, and the extracted information converted to a standard internal representation. A number of population analysis algorithms have been implemented as a proof of principle. In addition, cclib is currently used as an input filter for two GUI applications that analyze output files: PyMOlyze and GaussSum. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

4,451 citations


Journal ArticleDOI
TL;DR: The implementation of various DFT functionals and many‐body techniques within highly efficient, stable, and versatile computer codes, which allow to exploit the potential of modern computer architectures are discussed.
Abstract: During the past decade, computer simulations based on a quantum-mechanical description of the interactions between electrons and between electrons and atomic nuclei have developed an increasingly important impact on solid-state physics and chemistry and on materials science—promoting not only a deeper understanding, but also the possibility to contribute significantly to materials design for future technologies. This development is based on two important columns: (i) The improved description of electronic many-body effects within density-functional theory (DFT) and the upcoming post-DFT methods. (ii) The implementation of the new functionals and many-body techniques within highly efficient, stable, and versatile computer codes, which allow to exploit the potential of modern computer architectures. In this review, I discuss the implementation of various DFT functionals [local-density approximation (LDA), generalized gradient approximation (GGA), meta-GGA, hybrid functional mixing DFT, and exact (Hartree-Fock) exchange] and post-DFT approaches [DFT + U for strong electronic correlations in narrow bands, many-body perturbation theory (GW) for quasiparticle spectra, dynamical correlation effects via the adiabatic-connection fluctuation-dissipation theorem (AC-FDT)] in the Vienna ab initio simulation package VASP. VASP is a plane-wave all-electron code using the projector-augmented wave method to describe the electron-core interaction. The code uses fast iterative techniques for the diagonalization of the DFT Hamiltonian and allows to perform total-energy calculations and structural optimizations for systems with thousands of atoms and ab initio molecular dynamics simulations for ensembles with a few hundred atoms extending over several tens of ps. Applications in many different areas (structure and phase stability, mechanical and dynamical properties, liquids, glasses and quasicrystals, magnetism and magnetic nanostructures, semiconductors and insulators, surfaces, interfaces and thin films, chemical reactions, and catalysis) are reviewed. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008

2,364 citations


Journal ArticleDOI
TL;DR: It is demonstrated that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms.
Abstract: A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both alpha- and beta-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies.

1,751 citations


Journal ArticleDOI
TL;DR: Compared to nonapproximated treatments, RI‐JK‐HF leads to large computational savings for quadruple zeta valence orbital bases and, in case of small to midsize systems, to significant savings for triple zetavalence bases.
Abstract: For elements H to Rn (except Lanthanides), a series of auxiliary basis sets fitting exchange and also Coulomb potentials in Hartree–Fock treatments (RI-JK-HF) is presented. A large set of small molecules representing nearly each element in all its common oxidation states was used to assess the quality of these auxiliary bases. For orbital basis sets of triple zeta valence and quadruple zeta valence quality, errors in total energies arising from the RI-JK approximation are below ∼1 meV per atom in molecular compounds. Accuracy of RI-JK-approximated HF wave functions is sufficient for being used for post-HF treatments like Moller–Plesset perturbation theory, MP2. Compared to nonapproximated treatments, RI-JK-HF leads to large computational savings for quadruple zeta valence orbital bases and, in case of small to midsize systems, to significant savings for triple zeta valence bases. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

526 citations


Journal ArticleDOI
TL;DR: An all‐atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose is presented.
Abstract: We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the alpha- and beta-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute-water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids.

470 citations


Journal ArticleDOI
TL;DR: The present results have shown that the cost effectiveness in the numerical basis sets implemented in the DFT code DMol3 is superior to that in Gaussian basis sets in terms of accuracy per computational cost.
Abstract: Binding energies of selected hydrogen bonded complexes have been calculated within the framework of density functional theory (DFT) method to discuss the efficiency of numerical basis sets implemented in the DFT code DMol3 in comparison with Gaussian basis sets. The corrections of basis set superposition error (BSSE) are evaluated by means of counterpoise method. Two kinds of different numerical basis sets in size are examined; the size of the one is comparable to Gaussian double zeta plus polarization function basis set (DNP), and that of the other is comparable to triple zeta plus double polarization functions basis set (TNDP). We have confirmed that the magnitudes of BSSE in these numerical basis sets are comparative to or smaller than those in Gaussian basis sets whose sizes are much larger than the corresponding numerical basis sets; the BSSE corrections in DNP are less than those in the Gaussian 6-311+G(3df,2pd) basis set, and those in TNDP are comparable to those in the substantially large scale Gaussian basis set aug-cc-pVTZ. The differences in counterpoise corrected binding energies between calculated using DNP and calculated using aug-cc-pVTZ are less than 9 kJ/mol for all of the complexes studied in the present work. The present results have shown that the cost effectiveness in the numerical basis sets in DMol3 is superior to that in Gaussian basis sets in terms of accuracy per computational cost.

442 citations


Journal ArticleDOI
TL;DR: The new generalized Born/volume integral (GB/VI) estimates the free energy of hydration as a classical electro static energy plus a cavitation energy that is not based upon atomic surface area (SA) used in GB/SA hydration models but on a VI London dispersion energy estimated from quantities already calculated in the classical electrostatic energy.
Abstract: A new generalized Born model for estimating the free energy of hydration is presented. The new generalized Born/volume integral (GB/VI) estimates the free energy of hydration as a classical electrostatic energy plus a cavitation energy that is not based upon atomic surface area (SA) used in GB/SA hydration models but on a VI London dispersion energy estimated from quantities already calculated in the classical electrostatic energy. The (relatively few) GB/VI model parameters are fitted to experimental data, and parameterizations for two different atomic partial charge models are presented. Comparison of the calculated and experimental free energies of hydration for 560 small molecules (both neutral and charged) shows good agreement (r(2) = 0.94).

417 citations


Journal ArticleDOI
TL;DR: Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation.
Abstract: Version 9 of the Amber simulation programs includes a new semi-empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many nanoseconds. The link atom approach used for treating the QM/MM boundary shows improved performance, and the user interface has been rewritten to bring the format into line with classical MD simulations. Support is provided for the PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi-empirical Hamiltonians as well as the self-consistent charge density functional tight binding (SCC-DFTB) method. Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

350 citations


Journal ArticleDOI
TL;DR: PULCHRA is introduced, a fast and robust method for the reconstruction of full‐atom protein models starting from a reduced protein representation that is particularly suitable as an intermediate step between coarse‐grained model‐based structure prediction and applications requiring an all‐atom structure.
Abstract: We introduce PULCHRA, a fast and robust method for the reconstruction of full-atom protein models starting from a reduced protein representation. The algorithm is particularly suitable as an intermediate step between coarse-grained model-based structure prediction and applications requiring an all-atom structure, such as molecular dynamics, protein-ligand docking, structure-based function prediction, or assessment of quality of the predicted structure. The accuracy of the method was tested on a set of high-resolution crystallographic structures as well as on a set of low-resolution protein decoys generated by a protein structure prediction algorithm TASSER. The method is implemented as a standalone program that is available for download from http://cssb.biology.gatech.edu/skolnick/ files/PULCHRA.

307 citations


Journal ArticleDOI
TL;DR: The time‐dependent density functional theory (TDDFT) method was carried out to investigate the hydrogen‐bonded intramolecular charge‐transfer (ICT) excited state of 4‐dimethylaminobenzonitrile (DMABN) in methanol (MeOH) solvent and demonstrated that the intermolecular hydrogen bond C≡N···HO is significantly strengthened in the TICT state.
Abstract: The time-dependent density functional theory (TDDFT) method was carried out to investigate the hydrogen-bonded intramolecular charge-transfer (ICT) excited state of 4-dimethylaminobenzonitrile (DMABN) in methanol (MeOH) solvent. We demonstrated that the intermolecular hydrogen bond C[triple bond]N...H-O formed between DMABN and MeOH can induce the C[triple bond]N stretching mode shift to the blue in both the ground state and the twisted intramolecular charge-transfer (TICT) state of DMABN. Therefore, the two components at 2091 and 2109 cm(-1) observed in the time-resolved infrared (TRIR) absorption spectra of DMABN in MeOH solvent were reassigned in this work. The hydrogen-bonded TICT state should correspond to the blue-side component at 2109 cm(-1), whereas not the red-side component at 2091 cm(-1) designated in the previous study. It was also demonstrated that the intermolecular hydrogen bond C[triple bond]N...H-O is significantly strengthened in the TICT state. The intermolecular hydrogen bond strengthening in the TICT state can facilitate the deactivation of the excited state via internal conversion (IC), and thus account for the fluorescence quenching of DMABN in protic solvents. Furthermore, the dynamic equilibrium of these electronically excited states is explained by the hydrogen bond strengthening in the TICT state.

Journal ArticleDOI
TL;DR: The adsorption and reaction energies are compared with the results from Møller‐Plesset second‐order perturbation theory with basis set extrapolation and errors due to missing self‐interaction correction are not affected.
Abstract: Ewald summation is used to apply semiempirical long-range dispersion corrections (Grimme, J Comput Chem 2006, 27, 1787; 2004, 25, 1463) to periodic systems in density functional theory. Using the parameters determined before for molecules and the Perdew-Burke-Ernzerhof functional, structure parameters and binding energies for solid methane, graphite, and vanadium pentoxide are determined in close agreement with observed values. For methane, a lattice constant a of 580 pm and a sublimation energy of 11 kJ mol−1 are calculated. For the layered solids graphite and vanadia, the interlayer distances are 320 pm and 450 pm, respectively, whereas the graphite interlayer energy is −5.5 kJ mol−1 per carbon atom and layer. Only when adding the semiempirical dispersion corrections, realistic values are obtained for the energies of adsorption of C4 alkenes in microporous silica (−66 to −73 kJ mol−1) and the adsorption and chemisorption (alkoxide formation) of isobutene on acidic sites in the micropores of zeolite ferrierite (−78 to −94 kJ mol−1). As expected, errors due to missing self-interaction correction as in the energy for the proton transfer from the acidic site to the alkene forming a carbenium ion are not affected by the dispersion term. The adsorption and reaction energies are compared with the results from Moller-Plesset second-order perturbation theory with basis set extrapolation. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008

Journal ArticleDOI
TL;DR: A series of fifteen aromaticity tests that can be used to analyze the advantages and drawbacks of a group of aromaticity descriptors are introduced and it is concluded that indices based on the study of electron delocalization in aromatic species are the most accurate among those examined.
Abstract: Aromaticity is a central chemical concept widely used in modern chemistry for the interpretation of molecular structure, stability, reactivity, and magnetic properties of many compounds. As such, its reliable prediction is an important task of computational chemistry. In recent years, many methods to quantify aromaticity based on different physicochemical properties of molecules have been proposed. However, the nonobservable nature of aromaticity makes difficult to assess the performance of the numerous existing indices. In the present work, we introduce a series of fifteen aromaticity tests that can be used to analyze the advantages and drawbacks of a group of aromaticity descriptors. On the basis of the results obtained for a set of ten indicators of aromaticity, we conclude that indices based on the study of electron delocalization in aromatic species are the most accurate among those examined in this work.

Journal ArticleDOI
TL;DR: CPHF is applied to the calculation of the polarizability α of LiF in different aggregation states: finite and infinite chains, slabs, and cubic crystal, and results compare well with those obtained with a saw‐tooth potential approach, previously implemented in CRYSTAL.
Abstract: The Coupled Perturbed Hartree-Fock (CPHF) scheme has been implemented in the CRYSTAL06 program, that uses a gaussian type basis set, for systems periodic in 1D (polymers), 2D (slabs), 3D (crystals) and, as a limiting case, 0D (molecules), which enables comparison with molecular codes. CPHF is applied to the calculation of the polarizability alpha of LiF in different aggregation states: finite and infinite chains, slabs, and cubic crystal. Correctness of the computational scheme for the various dimensionalities and its numerical efficiency are confirmed by the correct trend of alpha: alpha for a finite linear chain containing N LiF units with large N tends to the value for the infinite chain, N parallel chains give the slab value when N is sufficiently large, and N superimposed slabs tend to the bulk value. CPHF results compare well with those obtained with a saw-tooth potential approach, previously implemented in CRYSTAL. High numerical accuracy can easily be achieved at relatively low cost, with the same kind of dependence on the computational parameters as for the SCF cycle. Overall, the cost of one component of the dielectric tensor is roughly the same as for the SCF cycle, and it is dominated by the calculation of two-electron four-center integrals.

Journal ArticleDOI
TL;DR: An adaptation of the density fitting scheme to translationally periodic systems is described, based on Fourier transformation techniques, and the results obtained with the periodic LMP2 method appear more reliable than the ones obtained using density functional theory.
Abstract: A computational technique for solving the MP2 equations for periodic systems using a local-correlation approach and implemented in the CRYSCOR code is presented. The Hartree-Fock solution provided by the CRYSTAL program is used as a reference. The motivations for the implementation of the new code are discussed, and the techniques adopted are briefly recalled. With respect to the original formulation (Pisani et al., J Chem Phys 2005, 122, 094113), many new features have been introduced in CRYSCOR to improve its efficiency and robustness. In particular, an adaptation of the density fitting scheme to translationally periodic systems is described, based on Fourier transformation techniques. Three examples of application are provided, concerning the CO(2) crystal, proton transfer in ice XI, and the adsorption of methane on MgO (001). The results obtained with the periodic LMP2 method for these systems appear more reliable than the ones obtained using density functional theory.

Journal ArticleDOI
TL;DR: An efficient method for calculating the free energy of solvation of a (macro)molecule embedded in a continuum solvent is presented, based on the fully analytical evaluation of the volume and spatial symmetry of the solvent that is displaced from around a solute atom by its neighboring atoms.
Abstract: An efficient method for calculating the free energy of solvation of a (macro)molecule embedded in a continuum solvent is presented. It is based on the fully analytical evaluation of the volume and spatial symmetry of the solvent that is displaced from around a solute atom by its neighboring atoms. The two measures of solvent displacement are combined in empirical equations to approximate the atomic (or self) electrostatic solvation energy and the solvent accessible surface area. The former directly yields the effective Born radius, which is used in the generalized Born (GB) formula to calculate the solvent-screened electrostatic interaction energy. A comparison with finite-difference Poisson data shows that atomic solvation energies, pair interaction energies, and their sums are evaluated with a precision comparable to the most accurate GB implementations. Furthermore, solvation energies of a large set of protein conformations have an error of only 1.5%. The solvent accessible surface area is used to approximate the nonpolar contribution to solvation. The empirical approach, called FACTS (Fast Analytical Continuum Treatment of Solvation), is only four times slower than using the vacuum energy in molecular dynamics simulations of proteins. Notably, the folded state of structured peptides and proteins is stable at room temperature in 100-ns molecular dynamics simulations using FACTS and the CHARMM force field.

Journal ArticleDOI
TL;DR: It is shown that the orientational preferences of the interfacial water molecules depend only on the local curvatures of the interface, and hence the molecules located at wells of concave curvature of the rippled surface prefer the same orientations as waters located at the surface of small apolar solutes.
Abstract: A new method is presented to identify the truly interfacial molecules at fluid/fluid interfaces seen at molecular resolution, a situation that regularly occurs in computer simulations. In the new method, the surface is scanned by moving a probe sphere of a given radius along a large set of test lines that are perpendicular to the plane of the interface. The molecules that are hit by the probe spheres are regarded as interfacial ones, and the position of the test spheres when they are in contact with the interfacial molecules give an estimate of the surface. The dependence of the method on various parameters, in particular, on the size of the probe sphere is discussed in detail. Based on the list of molecules identified as truly interfacial ones, two measures of the molecular scale roughness of the surface are proposed. The bivariate distribution of the lateral and normal distances of two points of the interface provides a full description of the molecular scale morphology of the surface in a statistical sense. For practical purposes two parameters related to the dependence of the average normal distance of two surface points on their lateral distance can be used. These two parameters correspond to the frequency and amplitude of the surface roughness, respectively. The new method is applied for the analysis of the molecular level structure of the liquid-vapor interface of water. As an immediate result of the application of the new method it is shown that the orientational preferences of the interfacial water molecules depend only on the local curvature of the interface, and hence the molecules located at wells of concave curvature of the rippled surface prefer the same orientations as waters located at the surface of small apolar solutes. The vast majority of the truly interfacial molecules are found to form a strongly percolating two-dimensional hydrogen bonded network at the surface, whereas no percolation is observed within the second molecular layer beyond the surface.

Journal ArticleDOI
TL;DR: Methods to search for low‐energy conformations, to generate a Boltzmann‐weighted ensemble of configurations, or to generate classical‐dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems.
Abstract: Methods to search for low-energy conformations, to generate a Boltzmann-weighted ensemble of configurations, or to generate classical-dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.

Journal ArticleDOI
TL;DR: A novel sequence representation that incorporates evolutionary information encoded using PSI‐BLAST profile‐based collocation of AA pairs is proposed that is shown to substantially improve the accuracy of the structural class prediction.
Abstract: Knowledge of structural classes is useful in understanding of folding patterns in proteins. Although existing structural class prediction methods applied virtually all state-of-the-art classifiers, many of them use a rela- tively simple protein sequence representation that often includes amino acid (AA) composition. To this end, we pro- pose a novel sequence representation that incorporates evolutionary information encoded using PSI-BLAST profile- based collocation of AA pairs. We used six benchmark datasets and five representative classifiers to quantify and compare the quality of the structural class prediction with the proposed representation. The best, classifier support vector machine achieved 61-96% accuracy on the six datasets. These predictions were comprehensively compared with a wide range of recently proposed methods for prediction of structural classes. Our comprehensive comparison shows superiority of the proposed representation, which results in error rate reductions that range between 14% and 26% when compared with predictions of the best-performing, previously published classifiers on the considered data- sets. The study also shows that, for the benchmark dataset that includes sequences characterized by low identity (i.e., 25%, 30%, and 40%), the prediction accuracies are 20-35% lower than for the other three datasets that include sequences with a higher degree of similarity. In conclusion, the proposed representation is shown to substantially improve the accuracy of the structural class prediction. A web server that implements the presented prediction method is freely available at http://biomine.ece.ualberta.ca/Structural_Class/SCEC.html.

Journal ArticleDOI
TL;DR: A new implementation of frozen‐density embedding (FDE) in the Amsterdam Density Functional (ADF) program package is presented and it is shown how this flexible setup can facilitate the application of FDE in multilevel simulations.
Abstract: A new implementation of frozen-density embedding (FDE) in the Amsterdam Density Functional (ADF) program package is presented. FDE is based on a subsystem formulation of density-functional theory (DFT), in which a large system is assembled from an arbitrary number of subsystems, which are coupled by an effective embedding potential. The new implementation allows both an optimization of all subsystems as a linear-scaling alternative to a conventional DFT treatment, the calculation of one active fragment in the presence of a frozen environment, and intermediate setups, in which individual subsystems are fully optimized, partially optimized, or completely frozen. It is shown how this flexible setup can facilitate the application of FDE in multilevel simulations. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Journal ArticleDOI
Koji Yasuda1
TL;DR: The algorithm to evaluate the Coulomb potential in the ab initio density functional calculation on the graphics processor unit (GPU) shows the considerable speedup over the commodity microprocessor.
Abstract: We propose the algorithm to evaluate the Coulomb potential in the ab initio density functional calculation on the graphics processor unit (GPU). The numerical accuracy required for the algorithm is investigated in detail. It is shown that GPU, which supports only the single-precision floating number natively, can take part in the major computational tasks. Because of the limited size of the working memory, the Gauss-Rys quadrature to evaluate the electron repulsion integrals (ERIs) is investigated in detail. The error analysis of the quadrature is performed. New interpolation formula of the roots and weights is presented, which is suitable for the processor of the single-instruction multiple-data type. It is proposed to calculate only small ERIs on GPU. ERIs can be classified efficiently with the upper-bound formula. The algorithm is implemented on NVIDIA GeForce 8800 GTX and the Gaussian 03 program suite. It is applied to the test molecules Taxol and Valinomycin. The total energies calculated are essentially the same as the reference ones. The preliminary results show the considerable speedup over the commodity microprocessor. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Journal ArticleDOI
TL;DR: FlexX, X‐Score, AutoDock, and BLEEP programs examined for their performance in binding free energy prediction in various situations including cocrystallized complex structures, cross docking of ligands to their non‐cocrystallized receptors, docking of thermally unfolded receptor decoys to their ligands, and complex structures with “randomized” ligand decoys.
Abstract: The prediction of the binding free energy between a ligand and a protein is an important component in the virtual screening and lead optimization of ligands for drug discovery. To determine the quality of current binding free energy estimation programs, we examined FlexX, X-Score, AutoDock, and BLEEP for their performance in binding free energy prediction in various situations including cocrystallized complex structures, cross docking of ligands to their non-cocrystallized receptors, docking of thermally unfolded receptor decoys to their ligands, and complex structures with "randomized" ligand decoys. In no case was there a satisfactory correlation between the experimental and estimated binding free energies over all the datasets tested. Meanwhile, a strong correlation between ligand molecular weight-binding affinity correlation and experimental predicted binding affinity correlation was found. Sometimes the programs also correctly ranked ligands' binding affinities even though native interactions between the ligands and their receptors were essentially lost because of receptor deformation or ligand randomization, and the programs could not decisively discriminate randomized ligand decoys from their native ligands; this suggested that the tested programs miss important components for the accurate capture of specific ligand binding interactions.

Journal ArticleDOI
TL;DR: The binding energies and geometries at the complete basis set (CBS) limit at the levels of the second order Møller–Plesset perturbation theory (MP2) and the coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] are evaluated.
Abstract: Using basis-set extrapolation schemes for a given data set, we evaluated the binding energies and geometries at the complete basis set (CBS) limit at the levels of the second order Moller–Plesset perturbation theory (MP2) and the coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)]. The systems include the hydrogen bonding (water dimer), aromatic interaction (benzene dimer), π–H interaction (benzene–water), cation–water, anion–water, π–cation interaction (cation–benzene), and π–anion interaction (anion–triazine). One extrapolation method is to exploit both BSSE-corrected and BSSE-uncorrected binding energies for the aug-cc-pVNZ (N = 2, 3, 4, …) basis set in consideration that both binding energies give the same CBS limit (CBSB). Another CBS limit (CBSC) is to use the commonly known extrapolation approach to exploit that the electron correlation energy is proportional to N−3. Since both methods are complementary, they are useful for estimating the errors and trend of the asymptotic values. There is no significant difference between both methods. Overall, the values of CBSC are found to be robust because of their consistency. However, for small N (in particular, for N = 2, 3), CBS is found to be slightly better for water–water interactions and cation–water and cation–benzene interactions, whereas CBS is found to be more reliable for bezene–water and anion–water interactions. We also note that the MP2 CBS limit value based on N = 2 and 3 combined with the difference between CCSD(T) and MP2 at N = 2 would be exploited to obtain a CCSD(T)/CBS value for aromatic–aromatic interactions and anion–π interactions, but not for cationic complexes. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

Journal ArticleDOI
TL;DR: A novel, provable, and efficient DEE‐like algorithm, called minimized‐DEE (MinDEE), is derived that guarantees that rotamers belonging to the minimized‐GMEC will not be pruned, while still pruning a combinatorial number of conformations.
Abstract: One of the main challenges for protein redesign is the efficient evaluation of a combinatorial number of candidate structures. The modeling of protein flexibility, typically by using a rotamer library of commonly-observed low-energy side-chain conformations, further increases the complexity of the redesign problem. A dominant algorithm for protein redesign is Dead-End Elimination (DEE), which prunes the majority of candidate conformations by eliminating rigid rotamers that provably are not part of the Global Minimum Energy Conformation (GMEC). The identified GMEC consists of rigid rotamers (i.e., rotamers that have not been energy-minimized) and is thus referred to as the rigid-GMEC. As a post-processing step, the conformations that survive DEE may be energy-minimized. When energy minimization is performed after pruning with DEE, the combined protein design process becomes heuristic, and is no longer provably accurate: a conformation that is pruned using rigid-rotamer energies may subsequently minimize to a lower energy than the rigid-GMEC. That is, the rigid-GMEC and the conformation with the lowest energy among all energy-minimized conformations (the minimized-GMEC) are likely to be different. While the traditional DEE algorithm succeeds in not pruning rotamers that are part of the rigid-GMEC, it makes no guarantees regarding the identification of the minimized-GMEC. In this paper we derive a novel, provable, and efficient DEE-like algorithm, called minimized-DEE (MinDEE), that guarantees that rotamers belonging to the minimized-GMEC will not be pruned, while still pruning a combinatorial number of conformations. We show that MinDEE is useful not only in identifying the minimized-GMEC, but also as a filter in an ensemble-based scoring and search algorithm for protein redesign that exploits energy-minimized conformations. We compare our results both to our previous computational predictions of protein designs and to biological activity assays of predicted protein mutants. Our provable and efficient minimized-DEE algorithm is applicable in protein redesign, protein-ligand binding prediction, and computer-aided drug design.

Journal ArticleDOI
TL;DR: This article presents a novel concept, the minimal molecular surface (MMS), for the theoretical modeling of biomolecules as a result of the surface free energy minimization when an apolar molecule is immersed in a polar solvent.
Abstract: This article presents a novel concept, the minimal molecular surface (MMS), for the theoretical modeling of biomolecules. The MMS can be viewed as a result of the surface free energy minimization when an apolar molecule, such as protein, DNA or RNA is immersed in a polar solvent. Based on the theory of differential geometry, the MMS is created via the mean curvature minimization of molecular hypersurface functions. A detailed numerical algorithm is presented for the practical generation of MMSs. Extensive numerical experiments, including those with internal and open cavities, are carried out to demonstrated the proposed concept and algorithms. The proposed MMS is typically free of geometric singularities. Application of the MMS to the electrostatic analysis is considered for a set of twenty six proteins. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

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TL;DR: In the context of biomolecular electrostatic calculations it is demonstrated that the MIB method generates substantially more accurate solutions of the PB equation than other established methods, thus providing a new level of reference values for such models.
Abstract: Implicit solvent models based on the Poisson-Boltzmann (PB) equation are frequently used to describe the interactions of a biomolecule with its dielectric continuum environment. A novel, highly accurate Poisson-Boltzmann solver is developed based on the matched interface and boundary (MIB) method, which rigorously enforces the continuity conditions of both the electrostatic potential and its flux at the molecular surface. The MIB based PB solver attains much better convergence rates as a function of mesh size compared to conventional finite difference and finite element based PB solvers. Consequently, highly accurate electrostatic potentials and solvation energies are obtained at coarse mesh sizes. In the context of biomolecular electrostatic calculations it is demonstrated that the MIB method generates substantially more accurate solutions of the PB equation than other established methods, thus providing a new level of reference values for such models. Initial results also indicate that the MIB method can significantly improve the quality of electrostatic surface potentials of biomolecules that are frequently used in the study of biomolecular interactions based on experimental structures.

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TL;DR: A new program for multilevel (QM/QM and/or QM/MM) approaches is presented that is able to combine different computational descriptions for different regions in a transparent and flexible manner, and two examples of using geometry optimizations with numerical gradients for excited‐state geometries.
Abstract: A new program for multilevel (QM/QM and/or QM/MM) approaches is presented that is able to combine different computational descriptions for different regions in a transparent and flexible manner. This program, designated QUILD (for QUantum-regions Interconnected by Local Descriptions), uses adapted delocalized coordinates (Int J Quantum Chem 2006, 106, 2536) for efficient geometry optimizations of equilibrium and transition-state structures, where both weak and strong coordinates may be present. The Amsterdam Density Functional (ADF) program is used for providing density functional theory and MM energies and gradients, while an interface to the ORCA program is available for including RHF, MP2, or semiempirical descriptions. The QUILD optimization setup reduces the number of geometry steps needed for the Baker test-set of 30 organic molecules by approximately 30% and for a weakly-bound test-set of 18 molecules by approximately 75% compared with the old-style optimizer in ADF, i.e., a speedup of roughly a factor four. We report two examples of using geometry optimizations with numerical gradients, for spin-orbit relativistic ZORA and for excited-state geometries. Finally, we show examples of its multilevel capabilities for a number of systems, including the multilevel boundary region of amino acid residues, an S(N)2 reaction in the gas-phase and in solvent, and a DNA duplex.

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TL;DR: This article presents a simple approach to introduce metal polarization effects (often termed image effects) in MD simulations by exploiting standard features of bio‐oriented MD codes such as the widely used GROMACS and NAMD.
Abstract: Combinatorial bio-techniques have demonstrated that proteins can be good and even selective binders for several inorganic surfaces, including metals. However, the understanding of the basic physical mechanisms that govern such interactions did not keep up with the success in these experiments. The comprehension of such mechanisms would greatly benefit from the computational investigation of the problem. Because of the complexity of the system, classical molecular dynamics simulations based on an atomistic description appear to be the best compromise between reliability and feasibility. For proteins interacting with metal surfaces, however, methodological improvements with respect to standard Molecular Dynamics (MD) of proteins are needed, since the polarization of the metal induced by the protein (and the surrounding water) is not generally negligible. In this article, we present a simple approach to introduce metal polarization effects (often termed image effects) in MD simulations by exploiting standard features of bio-oriented MD codes such as the widely used GROMACS and NAMD. Tests to show the reliability of the proposed methods are presented, and the results for a model application showing the importance of image effects are also discussed.

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TL;DR: This review surveyed quantum mechanical descriptions on how these states are affected by spin‐ orbit coupling and attempted to provide a conceptual framework with which to think about spin‐orbit coupling and its applications.
Abstract: In accounting for the magnetic properties of discrete and extended compounds with unpaired spins, it is crucial to know the nature of their ground and low-lying excited states. In this review we surveyed quantum mechanical descriptions on how these states are affected by spin-orbit coupling and attempted to provide a conceptual framework with which to think about spin-orbit coupling and its applications.

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TL;DR: The results indicate that the truncation of the MIE at the two‐body level can be an accurate, computationally nondemanding approximation to the configurational entropy of anharmonic internal degrees of freedom.
Abstract: Changes in the configurational entropies of molecules make important contributions to free energies of reaction for processes such as protein-folding, noncovalent association, and conformational change. However, obtaining entropy from molecular simulations represents a long-standing computational challenge. Here, two recently introduced approaches, the nearest-neighbor (NN) method and the mutual-information expansion (MIE), are combined to furnish an efficient and accurate method of extracting the configurational entropy from a molecular simulation to a given order of correlations among the internal degrees of freedom. The resulting method takes advantage of the strengths of each approach. The NN method is entirely nonparametric (i.e., it makes no assumptions about the underlying probability distribution), its estimates are asymptotically unbiased and consistent, and it makes optimum use of a limited number of available data samples. The MIE, a systematic expansion of entropy in mutual information terms of increasing order, provides a well-characterized approximation for lowering the dimensionality of the numerical problem of calculating the entropy of a high-dimensional system. The combination of these two methods enables obtaining well-converged estimations of the configurational entropy that capture many-body correlations of higher order than is possible with the simple histogramming that was used in the MIE method originally. The combined method is tested here on two simple systems: an idealized system represented by an analytical distribution of 6 circular variables, where the full joint entropy and all the MIE terms are exactly known; and the R,S stereoisomer of tartaric acid, a molecule with 7 internal-rotation degrees of freedom for which the full entropy of internal rotation has been already estimated by the NN method. For these two systems, all the expansion terms of the full MIE of the entropy are estimated by the NN method and, for comparison, the MIE approximations up to 3rd order are also estimated by simple histogramming. The results indicate that the truncation of the MIE at the 2-body level can be an accurate, computationally non-demanding approximation to the configurational entropy of anharmonic internal degrees of freedom. If needed, higher-order correlations can be estimated reliably by the NN method without excessive demands on the molecular-simulation sample size and computing time.