Performance of density functionals for the structure and energetics of (M–O)0,± (M=Al,Si, Sc–Zn)

We report the results of the performance of 20 exchange–correlation functionals of density functional theory (DFT) in the structure (Metal–Oxygen bond length) and energetical properties (bond dissociation energy, adiabatic ionisation energy, and adiabatic electron affinity) of twelve metal monoxides (M–O, M=Al, Si, Sc–Zn). The calculated results show that the selected DFT functionals have the ability to reproduce the M–O bond length with a mean deviation of 0.01–0.05 Å, the energy values are reproduced with a mean deviation of 0.20–1.00?eV. In general, the functionals with significant HF exchange show decent performance in the calculation of bond length and harmonic vibrational frequency. These functionals show poor performance in energetics. Our calculated results show that the M06-L, B3LYP, and TPSSh functionals give good performance in both structure and energetical properties of metal monoxides. These functionals are recommended for the studies of structure and energetics in metal oxide systems. Further, our studies indicate that M06-L can be used for the studies in larger molecular systems. Among the 20 DFT functionals, the recently developed N12 functional gives poor performance in the studies of metal monoxides. Hence this functional is not recommended for the studies of structure and energetics in metal oxide systems.     

Functional group based Ligand binding affinity scoring function at atomic environmental level

Use of knowledge based scoring function (KBSF) for virtual screening and molecular docking has become an established method for drug discovery. Lack of a precise and reliable free energy function that describes several interactions including water-mediated atomic interaction between amino-acid residues and ligand makes distance based statistical measure as the only alternative. Till now all the distance based scoring functions in KBSF arena use atom singularity concept, which neglects the environmental effect of the atom under consideration. We have developed a novel knowledge-based statistical energy function for protein-ligand complexes which takes atomic environment in to account hence functional group as a singular entity. The proposed knowledge based scoring function is fast, simple to construct, easy to use and moreover it tackle the existing problem of handling molecular orientation in active site pocket. We have designed and used Functional group based Ligand retrieval (FBLR) system which can identify and detect the orientation of functional groups in ligand. This decoy searching was used to build the above KBSF to quantify the activity and affinity of high resolution protein-ligand complexes. We have proposed the probable use of these decoys in molecular build-up as a de-novo drug designing approach. We have also discussed the possible use of the said KSBF in pharmacophore fragment detection and pseudo center based fragment alignment procedure.     

Synthesis and density functional theoretical study of steroidal spiro-triazolidinone

The reaction of 3beta-chloro-5alpha-cholestan-6-one semicarbazone 1 with hydrogen peroxide at 0 degrees C gives 3beta-chloro-5alpha-cholestan-6-spiro-1',2',4'-triazolidine-3'-one 2 as a product. The structural assignment of the product was confirmed on the basis of its elemental, analytical and spectral data. The ab initio calculations were performed by using density functional theory (DFT) at B3LYP/6-31G* basis set in order to describe a free radical reaction mechanism. The reaction proceeds through two radical intermediates formation. The mechanism of the reaction was explained by using frontier molecular orbital (FMO), spin electronic density map, encoded electrostatic potential map and atomic charges. It was found that the localization of frontier orbitals and the flow of atomic charges of all the calculated structures support the present reaction mechanism. The molecular properties like total energy, dipole moment and hardness of each optimized structure, were also explained. Stability of all the optimized structures in this study was supported by their respective fundamental frequencies and energy minima.     

Calculation of the free energy of association for protein complexes.

We have developed a method for calculating the association energy of quaternary complexes starting from their atomic coordinates. The association energy is described as the sum of two solvation terms and an energy term to account for the loss of translational and rotational entropy. The calculated solvation energy, using atomic solvation parameters and the solvent accessible surface areas, has a correlation of 96% with experimentally determined values. We have applied this methodology to examine intermediates in viral assembly and to assess the contribution isomerization makes to the association energy of molecular complexes. In addition, we have shown that the calculated association can be used as a predictive tool for analyzing modeled molecular complexes.     

A computational approach to studying monomer selectivity towards the template in an imprinted polymer

A computational approach was proposed to study monomer–template interactions in a molecularly imprinted polymer (MIP) in order to gain insight at the molecular level into imprinting polymer selectivity, regarding complex formation between template and monomer at the pre-polymerisation step. This is the most important step in MIP preparation. In the present work, chlorphenamine (CPA), diphenhydramine (DHA) and methacrylic acid (MAA), were chosen as the template, non-template, and monomer, respectively. The attained complexes were optimised, and changes in the interaction energies, atomic charges, IR spectroscopy results, dipole moment, and polarisability were studied. The effects of solvent on template–monomer interactions were also investigated. According to a survey of the literature, this is the first work in which dipole moment and polarisability were used to predict the types of interactions existing in pre-polymerisation complexes. In addition, the density functional tight-binding (DFTB) method, an approximate version of the density functional theory (DFT) method that was extended to cover the London dispersion energy, was used to calculate the interaction energy.     

Fluctuations and correlations in crystalline protein dynamics: a simulation analysis of staphylococcal nuclease

Understanding collective motions in protein crystals is likely to furnish insight into functional protein dynamics and will improve models for refinement against diffraction data. Here, four 10 ns molecular dynamics simulations of crystalline Staphylococcal nuclease are reported and analyzed in terms of fluctuations and correlations in atomic motion. The simulation-derived fluctuations strongly correlate with, but are slightly higher than, the values derived from the experimental B-factors. Approximately 70% of the atomic fluctuations are due to internal protein motion. For 65% of the protein atoms the internal fluctuations converge on the nanosecond timescale. Convergence is much slower for the elements of the interatomic displacement correlation matrix--of these, >80% converge within 1 ns for interatomic distances less, approximately <6 A, but only 10% for separations approximately =12 A. Those collective motions that converged on the nanosecond timescale involve mostly correlations within the beta-barrel or between alpha-helices of the protein. The R-factor with the experimental x-ray diffuse scattering for the crystal, which is determined by the displacement variance-covariance matrix, decreases to 8% after 10 ns simulation. Both the number of converged correlation matrix elements and the R-factor depend logarithmically on time, consistent with a model in which the number of energy minima sampled depends exponentially on the maximum energy barrier crossed. The logarithmic dependence is also extrapolated to predict a convergence time for the whole variance-covariance matrix of approximately 1 micros.     

New ultrasoft pseudopotentials for the study of silicates

New ultra-soft pseudopotentials (UPS's) for Si and O suitable for studies of silicate materials are reported. The performance of the new USP's in density functional calculations on a number of model systems is documented and compared both to observed properties and to those computed in highly converged all-electron calculations. The new USP's are significantly more reliable and accurate than thos previsouly developed and widely distributed. With the new USP's computed structural parameters follow well establised trends with regard to local and gradient corrected treatments of exchange and correlation. The correct order of stability of the α-quartz and sodalite structures is also reproduced although the energy difference is not in quantitative agreement with the all-electron calculations. A new Al USP is also generated and its performance in calculations on α-alumina documented. The importance of consistent treatments of exchange and correlation for core and valence electrons is established.     

Dynamic properties, electronic structure and functional activity of radioprotectors]

The methods of molecular dynamics and quantum chemistry were used to study the correlation between the functional activity of radioprotectors and their dynamic properties and atomic charges. It is shown that electrostatic interactions determine the correlation between the dynamics and functional activity of radioprotectors. The effects of conformation dynamics of aminothiols on the functions of radioprotectors is discussed.     

蛋白质-蛋白质对接中打分函数的研究

通过分析蛋白质－蛋白质间的静电、疏水作用和熵效应与相对于晶体结构的蛋白质主链原子的均方根偏差（RMSD）的相关性,定量地考查了它们在蛋白质－蛋白质对接中作为打分函数评价近天然构象的能力。对7个蛋白质复合物体系的分析表明,就水化能而言,原子接触势模型（ACE）优于原子水化参数模型（ASP）,且修正的ACE模型具有更好的评价近天然构象的能力;水化能与静电能结合对评价能力有进一步的提高。最后,我们将静电和修正的ACE水化能结合作为打分函数用于36个蛋白质复合物体系的对接研究,进一步证实了这两种能量项的组合能有效地将近天然结构从分子对接模式中区分出来。     

Systematic,spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

Understanding biological systems at the level of their relational (emergent) molecular properties in functional protein networks relies on imaging methods, able to spatially resolve a tissue or a cell as a giant, non‐random, topologically defined collection of interacting supermolecules executing myriads of subcellular mechanisms. Here, the development and findings of parameter‐unlimited functional super‐resolution microscopy are described—a technology based on the fluorescence imaging cycler (IC) principle capable of co‐mapping thousands of distinct biomolecular assemblies at high spatial resolution and differentiation (<40 nm distances). It is shown that the subcellular and transcellular features of such supermolecules can be described at the compositional and constitutional levels; that the spatial connection, relational stoichiometry, and topology of supermolecules generate hitherto unrecognized functional self‐segmentation of biological tissues; that hierarchical features, common to thousands of simultaneously imaged supermolecules, can be identified; and how the resulting supramolecular order relates to spatial coding of cellular functionalities in biological systems. A large body of observations with IC molecular systems microscopy collected over 20 years have disclosed principles governed by a law of supramolecular segregation of cellular functionalities. This pervades phenomena, such as exceptional orderliness, functional selectivity, combinatorial and spatial periodicity, and hierarchical organization of large molecular systems, across all species investigated so far. This insight is based on the high degree of specificity, selectivity, and sensitivity of molecular recognition processes for fluorescence imaging beyond the spectral resolution limit, using probe libraries controlled by ICs. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.     

Protein interactions and dynamics probed by quantum chemistry, computer simulations and neutron experiments

We review some recent experiments and calculations on aspects of the structure and dynamics of proteins and related systems. The use of quantum chemical techniques to determine geometries and energies of supramolecular complexes of biological interest is illustrated, and the concomitant development of empirical energy functions for use in protein simulations outlined. We describe how simulations of crystalline peptides and amino-acids using an empirical force field can be combined with appropriate coherent and incoherent inelastic neutron scattering experiments to elucidate the characteristics of lattice vibrations and diffusive atomic motions in the crystals. The application of molecular dynamics simulations to the interpretation of incoherent neutron scattering experiments on proteins is examined and the resulting ideas on the general characteristics of protein motion discussed in terms of their functional implications.     

Discrimination of near-native protein structures from misfolded models by empirical free energy functions

Free energy potentials, combining molecular mechanics with empirical solvation and entropic terms, are used to discriminate native and near-native protein conformations from slightly misfolded decoys. Since the functional forms of these potentials vary within the field, it is of interest to determine the contributions of individual free energy terms and their combinations to the discriminative power of the potential. This is achieved in terms of quantitative measures of discrimination that include the correlation coefficient between RMSD and free energy, and a new measure labeled the minimum discriminatory slope (MDS). In terms of these criteria, the internal energy is shown to be a good discriminator on its own, which implies that even well-constructed decoys are substantially more strained than the native protein structure. The discrimination improves if, in addition to the internal energy, the free energy expression includes the electrostatic energy, calculated by assuming non-ionized side chains, and an empirical solvation term, with the classical atomic solvation parameter model providing slightly better discrimination than a structure-based atomic contact potential. Finally, the inclusion of a term representing the side chain entropy change, and calculated by an established empirical scale, is so inaccurate that it makes the discrimination worse. It is shown that both the correlation coefficient and the MDS value (or its dimensionless form) are needed for an objective assessment of a potential, and that together they provide much more information on the origins of discrimination than simple inspection of the RMSD-free energy plots.     

Understanding atomic bonding and electronic distributions of a DNA molecule using DFT calculation and BOLS-BC model

Deoxyribonucleic acid (DNA) is an important molecule that has been extensively researched, mainly due to its structure and function. Herein, we investigated the electronic behavior of the DNA molecule containing 1008 atoms using density functional theory. The bond-charge (BC) model shows the relationship between charge density and atomic strain. Besides, the model mentioned above is combined with the bond-order-length-strength (BOLS) notion to calculate the atomic cohesive energy, the bond energy, and the local bond strain of the DNA chain. Using the BOLS-BC model, we were able to obtain information on the bonding features of the DNA chain and better comprehend the associated properties of electrons in biological systems. Consequently, this report functions as a theoretical reference for the precise regulation of the electrons and the bonding states of biological systems.     

Facile and Efficient Atomic Hydrogenation Enabled Black TiO2 with Enhanced Photo‐Electrochemical Activity via a Favorably Low‐Energy‐Barrier Pathway

Black TiO₂ has demonstrated a great potential for a variety of renewable energy technologies. However, its practical application is heavily hindered due to lack of efficient hydrogenation methods and a deeper understanding of hydrogenation mechanisms. Here, a simple and straightforward hot wire annealing (HWA) method is presented to prepare black TiO₂ (H–TiO₂) nanorods with enhanced photo‐electrochemical (PEC) activity by means of atomic hydrogen [H]. Compared to conventional molecular hydrogen approaches, the HWA shows remarkable effectiveness without any detrimental side effects on the device structure, and simultaneously the photocurrent density of H–TiO₂ reaches 2.5 mA cm^?2 (at 1.23 V vs reversible hydrogen electrode (RHE)). Due to the controllable and reproducible [H] flux, the HWA can be developed as a standard hydrogenation method for black TiO₂. Meanwhile, the relationships between the wire temperatures, structural, optical, and photo‐electrochemical properties are systematically investigated to verify the improved PEC activity. Furthermore, the density functional theory (DFT) study provides a comprehensive insight not only into the highly efficient mechanism of the HWA approach but also its favorably low‐energy‐barrier hydrogenation pathway. The findings will have a profound impact on the broad energy applications of H–TiO₂ and contribute to the fundamental understanding of its hydrogenation.     

When identical functional groups are not identical: A DFT study of the effects of molecular environment on sulfur K-edge X-ray absorption spectra

Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have been used to elucidate differences in the sulfur K-edge spectra of three pairs of related compounds: methionine and , cystine and (±)6-thioctic amide, and (Me)₂SO₃ and (CH₂)₂SO₃. TD-DFT is shown to accurately reproduce all the experimental XAS spectra. The 2 eV energy difference in the sulfur K-edge rising edge position between methionine and trimethylsulfonium is shown to derive from changes in bonding rather than the increase in effective nuclear charge. A similar insensitivity to effective nuclear charge is found in the XAS spectra of cystine and (±)6-thioctic amide. These surprising results are traced back to the fact that XAS spectra reflect orbital energy differences, rather than a measure of the atomic potential. The change in atomic potential following oxidation or reduction affects the core and valence orbitals almost equally. In all cases DFT calculations showed that the dramatic differences in sulfur K-edge spectra found between functional groups in alternative molecular environments derive from the variations in orbital mixing and energies following from bonding. However, XAS rising-edge energy positions have a near linear correlation with oxidation state. This is attributed to the fact that bond strength typically increases with oxidation state. Therefore, although XAS rising-edge energies are an approximate measure of the oxidation state of the absorbing atom, it is important to recognize that the correlation of XAS edge energy with effective nuclear charge is not direct. This result is finally applied to the question of quantitative sulfur speciation in complex materials of chemical, biological, or geological origin.     

Fluorination of BC3 nanotubes: DFT studies

We have studied the adsorption of atomic and molecular fluorines on a BC₃ nanotube by using density functional calculations. It was found that the adsorption of atomic fluorine on a C atom of the tube surface is energetically more favorable than that on a B atom by about 0.97 eV. The adsorption of atomic fluorine on both C and B atoms significantly affects the electronic properties of the BC₃ tube. The HOMO-LUMO energy gap is considerably reduced from 2.37 to 1.50 and 1.14 eV upon atomic F adsorption on B and C atoms, respectively. Molecular fluorine energetically tends to be dissociated on B atoms of the tube surface. The associative and dissociative adsorption energies of F₂ were calculated to be about ?0.42 and ?4.79 eV, respectively. Electron emission density from BC₃ nanotube surface will be increased upon both atomic and molecular fluorine adsorptions due to work function decrement.     

Diffusional behavior and guest conformational analysis of hexadecane-1,16-diol and hexadecane in urea crystal model via molecular dynamics simulation approach

Diffusion at the atomic or molecular level is a source of many physical, chemical, and biological processes taking place in plentiful materials. This work is an endeavor toward investigating the diffusional behavior of two different type of guests, hexadecane-1,16-diol and hexadecane enclathration in urea tunnel architecture, whereby the correlation of the diffusion mechanism with the guest’s structural and conformational properties is explored. To carry out this study, molecular dynamics simulation approach is adopted. It is found that hexadecane-1,16-diol exhibit slower diffusion with an average diffusion coefficient value \( \sim 1.83\times {10}^{-10} \), where hexadecane diffuse more rapidly with an average diffusion coefficient value \( \sim 2.58\times {10}^{-9} \). It is also observed that the structural properties influence the guest’s travel distance and torsion angle distribution of the trans and gauche conformational proportion. Furthermore, the observed high energy barrier accounted for hexadecane-1,16-diol and low energy barrier for hexadecane along urea tunnel systems was analyzed. The comparison of our obtained results are in close agreement with the available experimental measurements, i.e., gauche proportion properties between two different guest molecules correlate well with Raman spectroscopy investigation on α,ω-dihalogenoalkane/urea inclusion compounds. Our calculations also successfully endorse the structure-property relation between the two systems.     

Molecular dynamics modeling of the sub-THz vibrational absorption of thioredoxin from <Emphasis Type="Italic">E. coli</Emphasis>

Sub-terahertz (THz) vibrational modes of the protein thioredoxin in a water environment were simulated using molecular dynamics (MD) in order to find the conditions needed for simulation convergence, improve the correlation between experimental and simulated absorption frequencies, and ultimately enhance the predictive capabilities of computational modeling. Thioredoxin from E. coli was used as a model molecule for protocol development and to optimize the simulation parameters. The empirically parameterized software packages Amber 8 and 10 were used in this work. Using atomic trajectories from the constant energy and volume MD simulations, thioredoxin’s sub-THz vibrational spectra and absorption coefficients were calculated in a quasi-harmonic approximation. An optimal production run length ∼100 ps was found, in agreement with experimental data on thioredoxin relaxation dynamics. At the same time, a new procedure was developed for averaging correlation matrices of atomic coordinates in MD simulations. In particular, the open source package ptraj was edited to improve a matrix-analyzing function. Averaging only six matrices gave much more consistent results, with absorption peak intensities exceeding those from the individual spectra and a rather good correlation between simulated vibrational frequencies and experimental data.     

Internal motion in protein crystal structures

The binding states of the substrates and the environment have significant influence on protein motion. We present the analysis of such motion derived from anisotropic atomic displacement parameters (ADPs) in a set of atomic resolution protein structures. Local structural motion caused by ligand binding as well as functional loops showing cooperative patterns of motion could be inferred. The results are in line with proposed protonation states, hydrogen bonding patterns and the location of distinctly flexible regions: we could locate the mobile active site loop in a virus integrase, distinguish the subdomains in RNAse A and hydroxynitrile lyase, and reconstruct the molecular architecture in a xylanase. We demonstrate that the ADP‐based motion analysis provides information at high level of detail and that the structural changes needed for substrate attachment or release may be derived from single X‐ray structures.     

Functionality maps of binding sites: a multiple copy simultaneous search method

A new method is proposed for determining energetically favorable positions and orientations for functional groups on the surface of proteins with known three-dimensional structure. From 1,000 to 5,000 copies of a functional group are randomly placed in the site and subjected to simultaneous energy minimization and/or quenched molecular dynamics. The resulting functionality maps of a protein receptor site, which can take account of its flexibility, can be used for the analysis of protein ligand interactions and rational drug design. Application of the method to the sialic acid binding site of the influenza coat protein, hemagglutinin, yields functional group minima that correspond with those of the ligand in a cocrystal structure.