Showing papers in "Journal of Molecular Modeling in 2014"
TL;DR: A set of novel models for allergen prediction utilizing amino acid E-descriptors, auto- and cross-covariance transformation, and several machine learning methods for classification are reported, including logistic regression (LR), decision tree (DT), naïve Bayes (NB), random forest (RF), multilayer perceptron (MLP) and k nearest neighbours (kNN).
Abstract: Allergy is an overreaction by the immune system to a previously encountered, ordinarily harmless substance--typically proteins--resulting in skin rash, swelling of mucous membranes, sneezing or wheezing, or other abnormal conditions. The use of modified proteins is increasingly widespread: their presence in food, commercial products, such as washing powder, and medical therapeutics and diagnostics, makes predicting and identifying potential allergens a crucial societal issue. The prediction of allergens has been explored widely using bioinformatics, with many tools being developed in the last decade; many of these are freely available online. Here, we report a set of novel models for allergen prediction utilizing amino acid E-descriptors, auto- and cross-covariance transformation, and several machine learning methods for classification, including logistic regression (LR), decision tree (DT), naive Bayes (NB), random forest (RF), multilayer perceptron (MLP) and k nearest neighbours (kNN). The best performing method was kNN with 85.3% accuracy at 5-fold cross-validation. The resulting model has been implemented in a revised version of the AllerTOP server (http://www.ddg-pharmfac.net/AllerTOP).
562 citations
TL;DR: Every reaction stage has a family of subsequent structures that are characterized not solely by their phenomenological behavior but also by informational properties of their electronic density distribution (localizability, order, uniformity).
Abstract: The course of the Diels-Alder reactions of cyclopentadiene and maleic anhydride were studied. Two reaction paths were modelled: endo- and exo-selective paths. All structures within the transient region were characterized and analyzed by means of geometrical descriptors, physicochemical parameters and information-theoretical measures in order to observe the linkage between chemical behavior and the carriage of information. We have shown that the information-theoretical characterization of the chemical course of the reaction is in complete agreement with its phenomenological behavior in passing from reactants to products. In addition, we were able to detect the main differences between the two reaction mechanisms. This type of informational analysis serves to provide tools to help understand the chemical reactivity of the two simplest Diels-Alder reactions, which permits the establishment of a connection between the quantum changes that molecular systems exert along reaction coordinates and standard physicochemical phenomenology. In the present study, we have shown that every reaction stage has a family of subsequent structures that are characterized not solely by their phenomenological behavior but also by informational properties of their electronic density distribution (localizability, order, uniformity). Moreover, we were able to describe the main differences between endo-adduct and exo-adduct pathways. With the advent of new experimental techniques, it is in principle possible to observe the structural changes in the transient regions of chemical reactions. Indeed, through this work we have provided the theoretical concepts needed to unveil the concurrent processes associated with chemical reactions.
296 citations
TL;DR: The results of the calculations show that cyclopropenylidene can insert into azetidine at its C–N or C–C bond, and allenes are the dominant product because the reaction is exothermic by 373.4 kJ/mol−1.
Abstract: The mechanism for the ring expansion reaction between cyclopropenylidene and azetidine was systematically investigated employing second-order Moller–Plesset perturbation theory (MP2) in order to better understand the reactivity of cyclopropenylidene with the four-membered ring compound azetidine. Geometry optimizations and vibrational analyses were performed for the stationary points on the potential energy surfaces of the system. The results of our calculations show that cyclopropenylidene can insert into azetidine at its C–N or C–C bond. From a kinetic viewpoint, it is easier for cyclopropenylidene to insert into the C–N bond of azetidine than into the C–C bond. During the first insertion step and the second ring-opening step, it forms spiro and carbene intermediates, respectively. In the following two H-transfer steps, the carbene intermediate forms allenes and alkynes, respectively, as products. From a thermodynamic perspective, allenes are the dominant product because the reaction is exothermic by 373.4 kJ/mol−1.
183 citations
TL;DR: The main goal of this study was to suggest guidelines for the rational drug design of new agonists of leptin, and identified hits could be a consistent starting point to carry out in vitro testing.
Abstract: Body weight control is a mechanism finely regulated by several hormonal, metabolic, and nervous pathways. The leptin receptor (Ob-R) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream, and under normal circumstances, circulating levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased concentrations lead to opposite effects. Therefore rational design of leptin agonists constitute an appealing challenge in the battle against obesity. In this study, we performed protein-protein docking among the re-built crystal structure of leptin and leptin binding domain (LBD). The obtained complex was used as a starting point to carry out nanosecond-scale molecular dynamics simulations to characterize the key regions in terms of physical-chemical features involved in the protein-protein interaction (dynamic site mapping filtered by means multivariate analysis) and used to carry out a HTVS. The main goal of this study was to suggest guidelines for the rational drug design of new agonists of leptin. Identified hits could be a consistent starting point to carry out in vitro testing.
146 citations
TL;DR: There is an overall general tendency for greater impact sensitivity as the estimated free space per molecule increases, and the nitramine sensitivities increase nearly linearly but only very gradually with free space.
Abstract: There is considerable evidence, which we discuss, indicating that compressibility and available free space in the crystal lattice are among the factors that govern the sensitivity of an explosive compound. Expanding and extending earlier work, we demonstrate, for 25 explosives, that there is an overall general tendency for greater impact sensitivity as the estimated free space per molecule increases. More specific relationships can be discerned by looking at subgroups of the compounds. The nitramine sensitivities, most of which are quite high, increase nearly linearly but only very gradually with free space. The nitroaromatics cover a wide range of sensitivities but all have an approximately similar intermediate level of free space. The remaining types of compounds show a reasonable sensitivity–free space relationship with one outlier: FOX-7 (1,1-diamino-2,2-dinitroethylene).
119 citations
TL;DR: A unified coarse-grained model of three major classes of biological molecules—proteins, nucleic acids, and polysaccharides—has been developed, based on the observations that the repeated units of biopolymers are highly polar and their charge distributions can be represented crudely as point multipoles.
Abstract: A unified coarse-grained model of three major classes of biological molecules—proteins, nucleic acids, and polysaccharides—has been developed. It is based on the observations that the repeated units of biopolymers (peptide groups, nucleic acid bases, sugar rings) are highly polar and their charge distributions can be represented crudely as point multipoles. The model is an extension of the united residue (UNRES) coarse-grained model of proteins developed previously in our laboratory. The respective force fields are defined as the potentials of mean force of biomacromolecules immersed in water, where all degrees of freedom not considered in the model have been averaged out. Reducing the representation to one center per polar interaction site leads to the representation of average site–site interactions as mean-field dipole–dipole interactions. Further expansion of the potentials of mean force of biopolymer chains into Kubo’s cluster-cumulant series leads to the appearance of mean-field dipole–dipole interactions, averaged in the context of local interactions within a biopolymer unit. These mean-field interactions account for the formation of regular structures encountered in biomacromolecules, e.g., α-helices and β-sheets in proteins, double helices in nucleic acids, and helicoidally packed structures in polysaccharides, which enables us to use a greatly reduced number of interacting sites without sacrificing the ability to reproduce the correct architecture. This reduction results in an extension of the simulation timescale by more than four orders of magnitude compared to the all-atom representation. Examples of the performance of the model are presented.
114 citations
TL;DR: This study has tested the performance of the UCA-FUKUI software by calculating the global and local reactivity indexes of a group of representative molecules and shows the existence of a high correlation between global parameters, but a weaker correlation between local parameters.
Abstract: A new software (UCA-FUKUI) has been developed to facilitate the theoretical study of chemical reactivity. This program can calculate global parameters like hardness, softness, philicities, and Fukui condensed functions, and also local parameters from the condensed functions. To facilitate access to the program we have developed a very easy-to-use interface. We have tested the performance of the software by calculating the global and local reactivity indexes of a group of representative molecules. Finite difference and frontier molecular orbital methods were compared and their correlation tested. Finally, we have extended the analysis to a set of ligands of importance in coordination chemistry, and the results are compared with the exact calculation. As a general trend, our study shows the existence of a high correlation between global parameters, but a weaker correlation between local parameters.
95 citations
TL;DR: The structural, mechanical, electronic, and optical properties of orthorhombic Bi2S3 and Bi2Se3 compounds have been investigated by means of first principles calculations and the calculated lattice parameters and internal coordinates are in very good agreement with the experimental findings.
Abstract: The structural, mechanical, electronic, and optical propertiesoforthorhombicBi2S3andBi2Se3compoundshave been investigated by means of first principles calculations. The calculated lattice parameters and internal coordinates are in very good agreement with the experimental findings. The elastic constants are obtained, then the secondary results such as bulk modulus, shear modulus, Young's modulus, Poisson's ratio, anisotropy factor, and Debye temperature of polycrys- talline aggregates are derived, and the relevant mechanical properties are also discussed.Furthermore, the bandstructures and optical properties such as real and imaginary parts of dielectric functions, energy-loss function, the effective num- ber of valance electrons, and the effective optical dielectric constant have been computed. We also calculated some non- linearities for Bi2S3 and Bi2Se3 (tensors of elasto-optical co- efficients) under pressure.
69 citations
TL;DR: Analysis indicated that variational effects are small over the whole temperature range, while tunneling effects are significant in the lower temperature range.
Abstract: The tautomerization pathways and kinetics of 1,5-diaminotetrazole (DAT) have been investigated by means of second-order Moller-Plesset perturbation theory (MP2) and coupled-cluster theory, with single and double excitations including perturbative corrections for triple excitations (CCSD(T)). Five possible tautomers, namely 4-hydro-1-amino-5-imino-tetrazole (a), 2,5-diamino-tetrazole (b), 1,5-diamino-tetrazole (c), 2-hydro-1-imino-5-amino-tetrazole (d), and 2,4-dihydro-1,5-diimino-tetrazole (e) were identified. The structures of the reactants, transition states, and products along with the tautomerism pathways were optimized by the MP2 method using the 6-311G** basis set, and the energies were refined using CCSD(T)/6-311G**. The minimum-energy path (MEP) information for DAT was obtained at the CCSD(T)/6-311G**//MP2/6-311G** level of theory. Therein, reaction 2 (c → b) is an amino-shift reaction, while reaction 1 (c → a), reaction 3 (c → d), reaction 4 (a → e), and reaction 5 (d → e) are reactions of hydrogen-shift tautomerization. The calculated results show that 2,5-diaminotetrazole (b) with the minimum energy (taking c as a standard) among five tautomers, is the energetically preferred tautomer of DAT in the gas phase. In addition, the energy barrier of reaction 2 is 71.65 kcal · mol−1 in the gas phase, while reaction 1 takes place more easily with an activation barrier of 61.53 kcal · mol−1 also as compared to 63.71 kcal · mol−1 in reaction 3. Moreover, the tautomerization of reaction 4 requires the largest energy barrier of 83.29 kcal · mol−1, which is obviously bigger than reaction 5 with a value of 73.78 kcal · mol−1. Thus, the hydrogen-shift of c to a is the easiest transformation, while the tautomerization of a to e is the hardest one. Again, the rate constants of tautomerization have been obtained by TST, TST/Eckart, CVT, CVT/SCT, and CVT/ZCT methods in the range 200-2500 K, and analysis indicated that variational effects are small over the whole temperature range, while tunneling effects are significant in the lower temperature range.
60 citations
TL;DR: New electronic structure descriptors which are Fukui indices are correlated to the radical scavenging of flavonoids and these indices are obtained at DFT/B3LYP level of chemical quantum theory.
Abstract: A QSAR model to predict the antioxidant activity of flavonoid compounds was developed. New electronic structure descriptors which are Fukui indices are correlated to the radical scavenging of flavonoids. These indices are obtained at DFT/B3LYP level of chemical quantum theory. The logIC50 experimental values of antioxidant activity are taken from the literature. The model is based on the multilinear regression method. Both experimental and calculated data of 36 flavonoids compounds were analyzed. A good correlation coefficient (R2 = 0.8159) is obtained and the antioxidant activities of test compounds are well predicted.
53 citations
TL;DR: An adamantane nanocrystal that is easily calculated with EMPIRE is shown, and it is shown that the concentration of adamantane in Na6(CO3(SO4)(SO4) is higher than in the case of Na2SO4, so its value can be calculated using EMPIRE.
Abstract: EMPIRE is a massively parallel semiempirical (NDDO) molecular-orbital program designed to scale well both on single multi-core nodes (using open MP) and on large clusters (using a hybrid open MP/MPI model). The program design and performance are discussed for single self-consistent-field calculations on up to 55,000 (the adamantane crystal shown in the graphic) atoms and on both single- and multi-node machines using either Windows 7 or Linux. EMPIRE currently carries out the full SCF calculation with no local approximations or other linear-scaling techniques. The single-node version is available free of charge to bona fide academic groups.
TL;DR: Density functional theory calculations were used in the theoretical investigation of the adsorption properties of sumanene towards molecules considered as common air pollutants: CO, CO2 and NH3, and showed that chemical interactions exist and that these are more important mostly on the convex side.
Abstract: Density functional theory calculations were used in the theoretical investigation of the adsorption properties of sumanene towards molecules considered as common air pollutants: CO, CO₂ and NH₃. The insignificant perturbation of sumanene after adsorption and the adsorption energies obtained indicate a physisorption mechanism. It was shown that, contrary to carbon nanotubes, sumanene is able to adsorb CO molecules, and that adsorption of CO₂ by sumanene is stronger than adsorption of CO₂ by C₆₀. To better understand the adsorption characteristics of sumanene, density of states and natural bond order analyses were performed, which showed that chemical interactions exist and that these are more important mostly on the convex side. Better adsorption properties were obtained for the concave side as adsorption is dictated by physisorption mechanisms due to the specific bowl-shaped geometry of sumanene, because of which more negative charge is located precisely on the concave side. Molecular electrostatic potential surfaces were also used in order to better locate the adsorption sites and gain additional details about adsorption.
TL;DR: It is suggested that cholesteryl hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions are not playing a crucial role.
Abstract: Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role.
TL;DR: This study has specifically focused on the dielectric properties of different graphene/h-BN/graphene including their hetero-structure counterparts, i.e., Boron- graphene/h
Abstract: A model of a nanoscale dielectric capacitor composed of a few dopants has been investigated in this study. This capacitor includes metallic graphene layers which are separated by an insulating medium containing a few h-BN layers. It has been observed that the elements from group IIIA of the periodic table are more suitable as dopants for hetero-structures of the {metallic graphene/hBN/metallic graphene} capacitors compared to those from groups IA or IIA. In this study, we have specifically focused on the dielectric properties of different graphene/h-BN/graphene including their hetero-structure counterparts, i.e., Boron-graphene/h-BN/Boron-graphene, Al-graphene/h-BN/Al-graphene, Mg-graphene/h-BN/Mg-graphene, and Be-graphene/h-BN/Be-graphene stacks for monolayer form of dielectrics. Moreover, we studied the multi dielectric properties of different (h-BN)n/graphene hetero-structures of Boron-graphene/(h-BN)n/Boron-graphene.
TL;DR: Aiming to understand the process of crystal lattice stabilization, a combination of technique has been used including X-ray diffraction, infrared spectroscopy and computational molecular modeling to synthesize, crystallize, and characterize the dimethoxy-chalcone C18H18O3.
Abstract: Chalcones are an important class of medicinal compounds and are known for taking part in various biological activities as in anti-inflammatory, anti-leishmania, antimitotic, and antiviral. Chemically, chalcones consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α,β-unsaturated carbonyl system. The wide action spectrum has attracted our attention to synthesize, crystallize, and characterize the dimethoxy-chalcone C18H18O3. Aiming to understand the process of crystal lattice stabilization, a combination of technique has been used including X-ray diffraction, infrared spectroscopy and computational molecular modeling. The theoretical calculations were carried out by the density functional method (DFT) with the M06-2X functional, with the 6-311+G(d,p) basis set. The vibrational wavenumbers were calculated and the scaled values were compared with experimental FT-IR spectrum. The intermolecular interactions were quantified and intercontacts in the crystal structure were analyzed using Hirshfeld surfaces. Bond distances and angles described by the X-ray diffraction and theoretical calculation are very similar. The C-H….O contacts contributing to assemble the supramolecular architecture are also responsible for the molecular structure assembly.
TL;DR: The adsorption of the molecules CO, CO2, and H2 on several ceria and zinc oxide surfaces was studied by means of periodical DFT calculations and compared with infrared frequency data to provide a firm foundation for novel process development in methanol synthesis from carbon oxides, steam reforming of meethanol for hydrogen production, and/or the water-gas shift reaction.
Abstract: The adsorption of the molecules CO, CO2, and H2 on several ceria and zinc oxide surfaces was studied by means of periodical DFT calculations and compared with infrared frequency data. The stable CeO2(111), CeO2(331), and ZnO(0001) perfect faces were the first substrates considered. Afterwards, the same surfaces with oxygen vacancies and a ZnO monolayer grown on Ceria(111) were also studied in order to compare the behaviors and reactivities of the molecules at those surfaces. The ceria surfaces were substantially more reactive than the ZnO surface towards the CO2 molecule. The highest adsorption energy for this molecule was obtained on the CeO2(111) surface with oxygen vacancies. The molecules CO and H2 both presented low or very low reactivities on all of the surfaces studied, although some reactivity was observed for the adsorption of CO onto the surfaces with oxygen vacancies, whereas H2 exhibited reactivity towards the CeO2(111) surface with oxygen vacancies. This work was performed to provide a firm foundation for novel process development in methanol synthesis from carbon oxides, steam reforming of methanol for hydrogen production, and/or the water-gas shift reaction.
TL;DR: It is shown that, beyond the relevance of the results for the structural and dynamical characterization of HAS conformations, the present methodology could be extended to other proteins in the PDB archive.
Abstract: Human serum albumin (HSA) is a biologically relevant protein that binds a variety of drugs and other small molecules. No less than 50 structures are deposited in the RCSB Protein Data Bank (PDB). Based on these structures, we first performed a clustering analysis. Despite the diversity of ligands, only two well defined conformations are detected, with a deviation of 0.46 nm between the average structures of the two clusters, while deviations within each cluster are smaller than 0.08 nm. Those two conformations are representative of the apoprotein and the HSA-myristate complex already identified in previous literature. Considering the structures within each cluster as a representative sample of the dynamical states of the corresponding conformation, we scrutinize the structural and dynamical differences between both conformations. Analysis of the fluctuations within each cluster set reveals that domain II is the most rigid one and better matches both structures. Then, taking this domain as reference, we show that the structural difference between both conformations can be expressed in terms of twist and hinge motions of domains I and III, respectively. We also characterize the dynamical difference between conformations by computing correlations and principal components for each set of dynamical states. The two conformations display different collective motions. The results are compared with those obtained from the trajectories of short molecular dynamics simulations, giving consistent outcomes. Let us remark that, beyond the relevance of the results for the structural and dynamical characterization of HAS conformations, the present methodology could be extended to other proteins in the PDB archive.
TL;DR: It was shown that the electrical conductance of the AlN sheet may be increased after the SO2 adsorption, being somewhat insensitive to the O3 adsorbent, Thus, the Aln sheet may selectively detect SO2 molecules in the presence of O3 molecules.
Abstract: Theoretical calculations focused on the ability of an AlN nanosheet to detect O3 and SO2 molecules based on the dispersion corrected B3LYP (B3LYP-D) and B97D density functionals. Equilibrium geometries, stabilities, and the electronic properties of O3 and SO2 adsorptions on the surface of an AlN sheet were explored. The adsorption energies were calculated to be about −17.80 and −21.51 kcal mol-1 at B3LYP-D level for O3 and SO2 corresponding to the most stable configurations, respectively. It was shown that the electrical conductance of the AlN sheet may be increased after the SO2 adsorption, being somewhat insensitive to the O3 adsorption. Thus, the AlN sheet may selectively detect SO2 molecules in the presence of O3 molecules.
TL;DR: High-resolution protein structures have been analyzed in the present study to delineate various aspects of C-H…pi interactions and the separation in the primary structure between donor and acceptor residues is found to be correlated to secondary structure type.
Abstract: C-H…pi interactions are a class of non-covalent interactions found in different molecular systems including organic crystals, proteins and nucleic acids. High-resolution protein structures have been analyzed in the present study to delineate various aspects of C-H…pi interactions. Additionally, to determine the extent to which redundancy of a database biases the outcome, two datasets differing from each other in the level of redundancy have been analyzed. On average, only one out of six {with C-H(Aro) group} or eight {with C-H(Ali) group} residues in a protein participate as C-H group donors. Neither the frequency of occurrence in proteins nor the number of C-H groups present in it is correlated to the propensity of an amino acid to participate in C-H…pi interactions. Most of the residues that participate in C-H…pi interactions are solvent-shielded. Solvent shielded nature of most of the C-H…pi interactions and prevalence of intra- as well as inter-secondary structural element C-H…pi interactions suggest that the contribution of these interactions to the enthalpy of folded form will be significant. The separation in the primary structure between donor and acceptor residues is found to be correlated to secondary structure type. Other insights obtained from this study include the presence of networks of C-H…pi interactions spanning multiple secondary structural elements. To our knowledge this has not been reported so far. A substantial number of residues involved in C-H…pi interactions are found in catalytic and ligand binding sites suggesting their possible role in maintaining active site geometry. No significant differences of C-H…pi interactions in the two datasets are found for any of the parameters/features analyzed.
TL;DR: The results of this investigation indicate that the SPLET mechanism can be a favored reaction pathway for all three radicals in all solvents, except for •OH in the aqueous solution.
Abstract: The M05-2X/6-311++G(d,p) and B3LYP-D2/6-311++G(d,p) models are used to evaluate scavenging potency of gallic acid. The hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET), and single electron transfer followed by proton transfer (SET-PT) mechanisms of gallic acid with some radicals (•OO−, •OH, and CH3OO•) were investigated using the corresponding thermodynamic quantities: bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA). Namely, the ΔHBDE, ΔHIP, and ΔHPA values of the corresponding reactions in some solvents (water, DMSO, pentylethanoate, and benzene) are investigated using an implicit solvation model (SMD). An approach based on the reactions enthalpies related to the examined mechanisms is applied. This approach shows that a thermodynamically favored mechanism depends on the polarity of reaction media and properties of free radical reactive species. The most acidic 4-OH group of gallic acid is the active site for radical inactivation. The results of this investigation indicate that the SPLET mechanism can be a favored reaction pathway for all three radicals in all solvents, except for •OH in the aqueous solution. In water, gallic acid can inactivate •OH by the HAT mechanism.
TL;DR: The study shows that various properties of sumanene could be finely tuned for the application in the areas closely related to the materials science, including organic electronics and materials science engineering.
Abstract: We investigated the effects of substitution on the sumanene benzylic CH2 groups with BH and NH groups using density functional theory computations. Our study shows that various properties of sumanene could be finely tuned for the application in the areas closely related to the materials science. Structural properties are significantly altered with such modifications and other properties as well. Charge distributions were evaluated through natural population analysis (NPA), while stability of investigated structures was investigated using quantum molecular descriptors. Using molecular orbital analysis further insight into the effects of substitution was obtained. Potential of sumanene as a candidate for application in the field of organic electronics is assessed through calculations of exciton binding energy. Non-linear optical properties of investigated structures were investigated using the first hyperpolarizability tensor. Special attention was paid to the aromaticity of sumanene. This property was evaluated employing NICS parameter while for detailed study of obtained results we used NBO and NBOdel analysis.
TL;DR: The calculated first-and second shell hydration numbers, water residence times, and free energies of hydration are consistent with experimental/theoretical values leading to a predictive modeling of f-elements compounds.
Abstract: The hydration free energies, structures, and dynamics of open- and closed-shell trivalent lanthanide and actinide metal cations are studied using molecular dynamics simulations (MD) based on a polarizable force field. Parameters for the metal cations are derived from an ab initio bottom-up strategy. MD simulations of six cations solvated in bulk water are subsequently performed with the AMOEBA polarizable force field. The calculated first-and second shell hydration numbers, water residence times, and free energies of hydration are consistent with experimental/theoretical values leading to a predictive modeling of f-elements compounds.
TL;DR: In this paper, the authors examined the absorption properties of pyran based on theoretical UV-visible absorp- tion spectra, with comparisons between TD-DFT using B3LYP, PBE, and TPSSH functionals with 6-31+G (d) and 6-311++G** basis sets.
Abstract: Dye-sensitized solar cells (DSSCs) have drawn great attention as low cost and high performance alternatives to conventional photovoltaic devices. The molecular design presented in this work is based on the use of pyran type dyes as donor based on frontier molecular orbitals (FMO) and theoretical UV-visible spectra in combination with squaraine type dyes as an acceptor. Density functional theory has been used to investigate several derivatives of pyran type dyes for a better dye design based on optimization of absorption, regen- eration, and recombination processes in gas phase. The fron- tier molecular orbital (FMO) of the HOMO and LUMO energy levels plays an important role in the efficiency of DSSCs. These energies contribute to the generation of exciton, charge transfer, dissociation and exciton recombina- tion. The computations of the geometries and electronic struc- tures for the predicted dyes were performed using the B3LYP/ 6-31+G** level of theory. The FMO energies (EHOMO, ELUMO) of the studied dyes are calculated and analyzed in the terms of the UV- visible absorption spectra, which have been examined using time-dependent density functional the- ory (TD-DFT) techniques. This study examined absorption properties of pyran based on theoretical UV- visible absorp- tion spectra, with comparisons between TD-DFT using B3LYP, PBE, and TPSSH functionals with 6-31+G (d) and 6-311++G** basis sets. The results provide a valuable guide for the design of donor-acceptor (D-A) dyes with high molar absorptivity and current conversionin DSSCs. The theoretical results indicated 4-(dicyanomethylene)-2-methyl-6-(p- dimethylaminostyryl)-4H-pyran dye (D2-Me) can be effec- tively used as a donor dye for DSSCs. This dye has a low energy gap by itself and a high energy gap with squaraine acceptor type dye, the design that reduces the recombination and improves the photocurrent generation in solar cell.
TL;DR: It is shown that massive parallelization of the 3D structure similarity search process on many-core GPU devices can reduce the execution time of the process, allowing it to be performed in real time.
Abstract: Searching for similar 3D protein structures is one of the primary processes employed in the field of structural bioinformatics. However, the computational complexity of this process means that it is constantly necessary to search for new methods that can perform such a process faster and more efficiently. Finding molecular substructures that complex protein structures have in common is still a challenging task, especially when entire databases containing tens or even hundreds of thousands of protein structures must be scanned. Graphics processing units (GPUs) and general purpose graphics processing units (GPGPUs) can perform many time-consuming and computationally demanding processes much more quickly than a classical CPU can. In this paper, we describe the GPU-based implementation of the CASSERT algorithm for 3D protein structure similarity searching. This algorithm is based on the two-phase alignment of protein structures when matching fragments of the compared proteins. The GPU (GeForce GTX 560Ti: 384 cores, 2GB RAM) implementation of CASSERT (“GPU-CASSERT”) parallelizes both alignment phases and yields an average 180-fold increase in speed over its CPU-based, single-core implementation on an Intel Xeon E5620 (2.40GHz, 4 cores). In this paper, we show that massive parallelization of the 3D structure similarity search process on many-core GPU devices can reduce the execution time of the process, allowing it to be performed in real time. GPU-CASSERT is available at: http://zti.polsl.pl/dmrozek/science/gpucassert/cassert.htm.
TL;DR: A new 3D graphical representation of DNA sequences is introduced, a generalization of the 2D-dynamic dynamic representation, which can be identified and correctly described by both 2D and 3D methods.
Abstract: A new 3D graphical representation of DNA sequences is introduced This representation is called 3D-dynamic representation It is a generalization of the 2D-dynamic dynamic representation The sequences are represented by sets of “material points” in the 3D space The resulting 3D-dynamic graphs are treated as rigid bodies The descriptors characterizing the graphs are analogous to the ones used in the classical dynamics The classification diagrams derived from this representation are presented and discussed Due to the third dimension, “the history of the graph” can be recognized graphically because the 3D-dynamic graph does not overlap with itself Specific parts of the graphs correspond to specific parts of the sequence This feature is essential for graphical comparisons of the sequences Numerically, both 2D and 3D approaches are of high quality In particular, a difference in a single base between two sequences can be identified and correctly described (one can identify which base) by both 2D and 3D methods
TL;DR: An evolution of the molecular simulator that, when moving to larger systems, instead of reducing the granularity of the dynamical treatment, exploits the extra power of the grid approach to end of preserving the detailed nature of theatomistic formulation of the interaction.
Abstract: Thanks to the advances in grid technologies, we are able to propose here an evolution of our molecular simulator that, when moving to larger systems, instead of reducing the granularity of the dynamical treatment (as is often done in molecular dynamics studies of such systems) exploits the extra power of the grid approach to the end of preserving the detailed nature of theatomistic formulation of the interaction. Key steps of such evolution are: (1) the assemblage of the interaction based on a composition of the ab initio intramolecular data and a portable parameterization of the intermolecular potential linking ab initio evaluation of intramolecular potentials and the partitioning of molecular polarizability; (2) the exploitation of an efficient coordinated porting and running of molecular dynamics codes on the European grid distributed computing infrastructure. As a prototype case study, the N-methylacetamide dimer in vacuo has been considered and the formation of possible conformers is analyzed.
TL;DR: This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, and molecular dynamics simulations, as well as work done to evaluate and confirm the active site of nsP 3.
Abstract: The recent emergence and re-emergence of alphaviruses, in particular the chikungunya virus (CHIKV), in numerous countries has invoked a worldwide threat to human health, while simultaneously generating an economic burden on affected countries. There are currently no vaccines or effective drugs available for the treatment of the CHIKV, and with few lead compounds reported, the vital medicinal chemistry is significantly more challenging. This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, and molecular dynamics simulations, as well as work done to evaluate and confirm the active site of nsP3. Virtual screening was carried out based on blind docking as well as focused docking, using the database of 1541 compounds from NCI Diversity Set II, to identify hit compounds for nsP3. The top hit compounds were further subjected to molecular dynamic simulations, yielding a greater understanding of the dynamic behavior of nsP3 and its complexes with various ligands, concurrently confirming the outcomes of docking, and establishing in silico lead compounds which target the CHIKV nsP3 enzyme.
TL;DR: Graphene growth on copper turns out to be a catalytic, thermally-activated process that nucleates from carbon monomers, proceeds by adsorption of carbon atoms, and is not self-limiting.
Abstract: In this work the growth of a graphene monolayer on copper substrate, as typically achieved via chemical vapor deposition of propene (C3H6), was investigated by first-principles and kinetic Monte Carlo calculations. A comparison between calculated C1s core-level binding energies and electron spectroscopy measurements showed that graphene nucleates from isolated carbon atoms adsorbed on surface defects or sub-superficial layers upon hydrocarbon fragmentation. In this respect, ab initio nudged elastic band simulations yield the energetic barriers characterizing the diffusion of elemental carbon on the Cu(111) surface and atomic carbon uptake by the growing graphene film. Our calculations highlight a strong interaction between the growing film edges and the copper substrate, indicative of the importance of the grain boundaries in the epitaxy process. Furthermore, we used activation energies to compute the reaction rates for the different mechanisms occurring at the carbon–copper interface via harmonic transition state theory. Finally, we simulated the long-time system growth evolution through a kinetic Monte Carlo approach for different temperatures and coverage. Our ab initio and Monte Carlo simulations of the out-of-equilibrium system point towards a growth model strikingly different from that of standard film growth. Graphene growth on copper turns out to be a catalytic, thermally-activated process that nucleates from carbon monomers, proceeds by adsorption of carbon atoms, and is not self-limiting. Furthermore, graphene growth seems to be more effective at carbon supersaturation of the surface—a clear fingerprint of a large activation barrier for C attachment. Our growth model and computational results are in good agreement with recent X-ray photoelectron spectroscopy experimental measurements.
TL;DR: A comparative study on six efficient optimization algorithms, containing two evolutionary algorithm (EA) and four particle swarm optimization (PSO)-based optimizers (SODock), which were implemented into the protein–ligand docking program AutoDock, and built a new fitness accuracy as the evaluation criterion that incorporates optimization accuracy, robustness, and efficiency.
Abstract: In protein–ligand docking, an optimization algorithm is used to find the best binding pose of a ligand against a protein target. This algorithm plays a vital role in determining the docking accuracy. To evaluate the relative performance of different optimization algorithms and provide guidance for real applications, we performed a comparative study on six efficient optimization algorithms, containing two evolutionary algorithm (EA)-based optimizers (LGA, DockDE) and four particle swarm optimization (PSO)-based optimizers (SODock, varCPSO, varCPSO-ls, FIPSDock), which were implemented into the protein–ligand docking program AutoDock. We unified the objective functions by applying the same scoring function, and built a new fitness accuracy as the evaluation criterion that incorporates optimization accuracy, robustness, and efficiency. The varCPSO and varCPSO-ls algorithms show high efficiency with fast convergence speed. However, their accuracy is not optimal, as they cannot reach very low energies. SODock has the highest accuracy and robustness. In addition, SODock shows good performance in efficiency when optimizing drug-like ligands with less than ten rotatable bonds. FIPSDock shows excellent robustness and is close to SODock in accuracy and efficiency. In general, the four PSO-based algorithms show superior performance than the two EA-based algorithms, especially for highly flexible ligands. Our method can be regarded as a reference for the validation of new optimization algorithms in protein–ligand docking.
TL;DR: A parameter library derived from the widely used parm99SB set from the AMBER program package is presented to facilitate future atomistic simulations of isolated amino acids in their zwitterionic form.
Abstract: Isolated amino acids play an important role in biochemistry and are therefore an interesting object of study. Atomistic molecular dynamics (MD) simulations can provide a high-resolution picture of the dynamic features of these species, especially in their biological environment. Unfortunately, most standard force field packages lack libraries for isolated amino acids in their zwitterionic form. Although several studies have used ad-hoc parameterizations for single amino acids, a consistent force-field parameter set for these molecules is still missing. Here, we present such a parameter library derived from the widely used parm99SB set from the AMBER program package. The parameter derivation for all 20 proteinogenic amino acids transparently followed established procedures with histidine treated in three different protonation states. All amino acids were subjected to MD simulations in four different forms for comparison: zwitterionic, N-teminally capped with acetyl, C-terminally capped with N-methyl, and capped at both termini. Simulation results show similarities between the different forms. Five zwitterionic amino acids-arginine, glutamate, glycine, phenylalanine, leucine-were simulated in a protein environment. Proteins and ligands generally retained their initial structure. The new parameter set will thus facilitate future atomistic simulations of these species.