Real Complexes Research Articles

On real quadric line complexes

We describe the topological types of the real parts of the Kummer surfaces associated with real three-dimensional quadric line complexes. The topological type of the real part of such a surface is shown to depend on the number of real singular points: it is determined by the number of such points if any exist, and otherwise the real part of the Kummer surface is either empty or consists of one or two tori.

Protein complex prediction based on k-connected subgraphs in protein interaction network

BackgroundProtein complexes play an important role in cellular mechanisms. Recently, several methods have been presented to predict protein complexes in a protein interaction network. In these methods, a protein complex is predicted as a dense subgraph of protein interactions. However, interactions data are incomplete and a protein complex does not have to be a complete or dense subgraph.ResultsWe propose a more appropriate protein complex prediction method, CFA, that is based on connectivity number on subgraphs. We evaluate CFA using several protein interaction networks on reference protein complexes in two benchmark data sets (MIPS and Aloy), containing 1142 and 61 known complexes respectively. We compare CFA to some existing protein complex prediction methods (CMC, MCL, PCP and RNSC) in terms of recall and precision. We show that CFA predicts more complexes correctly at a competitive level of precision.ConclusionsMany real complexes with different connectivity level in protein interaction network can be predicted based on connectivity number. Our CFA program and results are freely available from http://www.bioinf.cs.ipm.ir/softwares/cfa/CFA.rar.

Drug–protein interactions assessed by fluorescence measurements in the real complexes and in model dyads

In the present work, a systematic fluorescence study on supramolecular systems using two serum albumins (HSA or BSA) as hosts and the nonsteroidal antiinflammatory drugs carprofen (CPF) or naproxen (NPX) as guests has been undertaken. In parallel, model dyads containing Tyr or Trp covalently linked to CPF or NPX have also been investigated. In HSA/(S)-CPF and BSA/(S)-CPF ( λ exc = 266 nm), at 1:1 M ratio, an important degree (more than 40%) of singlet–singlet energy transfer (SSET) was observed to take place. The distance ( r) calculated for energy transfer from the SAs to (S)-CPF through a FRET mechanism was found to be ca. 21 Å. In the case of HSA/(S)-NPX and BSA/(S)-NPX, energy transfer occurred to a lower extent (ca. 7%), and r was determined as ca. 24 Å. In order to investigate the possible excited state interactions between bound ligands and the relevant amino acids present in the protein binding sites, four pairs of model dyads were designed and synthesised, namely ( S, S)-TyrCPF, ( S, R)-TyrCPF, ( S, S)-TrpCPF, ( S, R)-TrpCPF, ( S, S)-TyrNPX, ( S, R)-TyrNPX, ( S, S)-TrpNPX and ( S, R)-TrpNPX. A complete SSET was observed from Tyr or Trp to CPF, since no contribution from the amino acids was present in the emission of the dyads. Likewise, a very efficient Tyr or Trp to NPX energy transfer was observed. Remarkably, in ( S, S)-TrpNPX and ( S, R)-TrpNPX a configuration-dependent reduction in the emission intensity was observed, revealing a strong and stereoselective intramolecular quenching. This effect can be attributed to exciplex formation and is dynamic in nature, as the fluorescence lifetimes were much shorter in ( S, R)- and ( S, S)-TrpNPX (1.5 and 3.1 ns, respectively) than in (S)-NPX (11 ns).

Identifying Protein Complexes Using Hybrid Properties

Protein complexes, integrating multiple gene products, perform all sorts of fundamental biological functions in cells. Much effort has been put into identifying protein complexes using computational approaches. A vast majority attempt to research densely connected regions in protein-protein interaction (PPI) network/graph. In this research, we try an alterative approach to analyze protein complexes using hybrid features and present a method to determine whether multiple (more than two) proteins from yeast can form a protein complex. The data set consists of 493 positive protein complexes and 9878 negative protein complexes. Every complex is represented by graph features, where proteins in the complex form a graph (web) of interactions, and features derived from biological properties including protein length, biochemical properties and physicochemical properties. These features are filtered and optimized by Minimum Redundancy Maximum Relevance method, Incremental Feature Selection and Forward Feature Selection, established through a prediction/identification model called Nearest Neighbor Algorithm. Jackknife cross-validation test is employed to evaluate the identification accuracy. As a result, the highest accuracy for the identification of the real protein complexes using filtered features is 69.17%, and feature analysis shows that, among the adopted features, graph features play the main roles in the determination of protein complexes.

ChemInform Abstract: Infrared Spectroscopy of Organometallic Ions in the Gas Phase: From Model to Real World Complexes

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Frontier Orbital Consistent Quantum Capping Potential (FOC-QCP) for Bulky Ligand of Transition Metal Complexes

Chemically reasonable models of PR3 (R = Me, Et, iPr, and tBu) were constructed to apply the post Hartree-Fock method to large transition metal complexes. In this model, R is replaced by the H atom including the frontier orbital consistent quantum capping potential (FOC-QCP) which reproduces the frontier orbital energy of PR3. The steric effect is incorporated by the new procedure named steric repulsion correction (SRC). To examine the performance of this FOC-QCP method with the SRC, the activation barriers and reaction energies of the reductive elimination reactions of C2H6 and H2 from M(R1)2(PR2(3))2 (M = Ni, Pd, or Pt; R1 = Me for R2 = Me, Et, or iPr, or R1 = H for R2 = tBu) were evaluated with the DFT[B3PW91], MP4(SDQ), and CCSD(T) methods. The FOC-QCP method reproduced well the DFT[B3PW91]- and MP4(SDQ)-calculated energy changes of the real complexes with PMe3. For more bulky phosphine, the SRC is important to present correct energy change, in which the MP2 method presents reliable steric repulsion correction like the CCSD(T) method because the systems calculated in the SRC do not include a transition metal element. The monomerization energy of [RhCl(PiPr3)2]2 and the coordination energies of CO, H2, N2, and C2H4 with [RhCl(PiPr3)2]2 were theoretically calculated by the CCSD(T) method combined with the FOC-QCP and the SRC. The CCSD(T)-calculated energies agree well with the experimental ones, indicating the excellent performance of the combination of the FOC-QCP with the SRC. On the other hand, the DFT[B3PW91]-calculated energies of the real complexes considerably deviate from the experimental ones.

An easy-to-use practical method to measure coincidence in the flow cytometer—The case of platelet–granulocyte complex determination

Cell complexes composed of two different cells labeled with different fluorophores can be detected as double positive events in the flow cytometer. Double positivity can originate not only from real complexes but from non-interacting coinciding cells as well. Coincidence has a high impact on the determination of the amount of platelet–granulocyte complexes since platelet concentration is in the orders of magnitude higher than that of the granulocytes. Mixtures of non-interacting fluorescent beads as well as EDTA anticoagulated or citrated blood samples were analyzed in the flow cytometer in the presence and absence of fluorescent beads at various dilutions. Experimental data were evaluated by mathematical means. The bead or platelet concentration dependence of double positivity was converted into linear functions using Poisson distribution. This linearised form contains information on the detection volume as well as on the presence/absence of dilution independent complexes. The presence of appropriate fluorescent beads in the blood sample makes possible to estimate the fraction of double positivity originating from coincidence if data collection is triggered by the granulocytes or by the fluorescent beads, alternatively. Mixing fluorescent beads into a blood sample is a simple experimental method to distinguish double positivity originating from real cell–cell complexes from the coincidence of cells in a flow cytometer, thus providing a tool for the determination of the real amount of cell–cell complexes.

Impact of coincidence on granulocyte–platelet complex determination by flow cytometry is evaluated by a novel computer simulation model of coincidence

Cell complexes composed of two different cells labeled with different fluorophores can be detected as double positive events in the flow cytometer. Double positivity can originate not only from real complexes but from non-interacting coinciding cells as well. Coincidence has a high impact on the determination of the amount of platelet–granulocyte complexes since platelet concentration is in the orders of magnitude higher than that of the granulocytes. A computer model has been developed to simulate coincidence in the flow cytometer to reveal the contribution of coincidence to the overestimation of the total amount of platelet–granulocyte complexes. Mixtures of non-interacting fluorescent beads as well as EDTA-anticoagulated blood samples were analyzed in the flow cytometer. An excellent fit was found between computer simulated and measured data pairs. Bead mixture in the flow cytometer and simulation of that resulted in 37.3 ± 1.3 and 35.7 ± 0.6% double positivity, respectively. 30.2 ± 4.3% double positivity was measured for EDTA-anticoagulated blood samples while simulation of that resulted in 28.3 ± 0.6%. Double positivity attributed to platelet–granulocyte complexes in slightly diluted blood samples might originate in coincidence and not from true complexes.

Infrared spectroscopy of organometallic ions in the gas phase: From model to real world complexes

Gas phase mid-infrared spectroscopy of molecular ions can nowadays be performed with high performance mass spectrometers coupled to free electron lasers (FEL). The wide and continuous tunability of highly intense FELs in the mid-infrared region can be exploited for performing infrared multiple photon dissociation (IRMPD) spectroscopy of molecular ions. This review will focus on gas phase IRMPD spectroscopic investigations aiming at probing the structure and the reactivity of transition metal complexes. The performance of infrared spectroscopy for characterizing the coordination mode of polydentate ligands and the spin state of the metal will be illustrated. Infrared spectroscopy has also been exploited to probe the reactivity of metal complexes, and a special attention will be given to the infrared spectroscopy of reactive intermediates.

Protein Coevolution and Isoexpression in Yeast Macromolecular Complexes

Previous studies in the yeast Saccharomyces cerevisiae have shown that genes encoding subunits of macromolecular complexes have similar evolutionary rates (K) and expression levels (E). Besides, it is known that the expression of a gene is a strong predictor of its rate of evolution (i.e., E and K are correlated). Here we show that intracomplex variation of subunit expression correlates with intracomplex variation of their evolutionary rates (using two different measures of dispersion). However, a similar trend was observed for randomized complexes. Therefore, using a mathematical transformation, we created new variables capturing intracomplex variation of both E and K. The values of these new compound variables were smaller for real complexes than for randomized ones. This shows that proteins in complexes tend to have closer expressivities (E) and K's simultaneously than in the randomly grouped genes. We speculate about the possible implications of this finding.

Toward a Clear-Cut Vision on the Origin of 2,6-Di(1,2,4-triazin-3-yl)pyridine Selectivity for Trivalent Actinides: Insights from Theory

Although BTP (2,6-di(1,2,4-triazin-3-yl)pyridine) has been widely evidenced as the most effective nitrogen ligand for the selective complexation of trivalent actinides from lanthanide counterparts, the origin of its selectivity is still an open question. Neither experimental data nor theoretical calculations have been able to rationalize the role of covalency in real experimental BTP complexes. We show herein with DFT calculations on [M(BTP)3]3+ (M = La, U, Cm, Gd) that, even if back-bonding effects are significant in the U-BTP bond, it is the contrast of donation on 6d and 5f Cm(III) orbitals that explains, at least in part, its selective complexation to BTP.

Molecular routes for spin cluster qubits

We report on real molecular complexes and propose strategies that explore the possibility of implementation of specific quantum computation architectures with molecular spin systems. We focus on Cr3+ carboxylate derivatives and use the Loss-DiVincenzo scheme as reference.

Analysis of angiogenesis usingin vitroexperiments and stochastic growth models

The global properties of vascular networks grown with an in vitro angiogenesis assay are compared quantitatively, using automated image analysis, with the global properties of networks obtained with discrete, stochastic growth models. The model classes that are investigated are invasion percolation and diffusion limited aggregation. By matching global properties to experimental data, one can infer which model classes and parameters are most reflective of angiogenesis in experimental cells. This sheds light on large-scale emergent properties of angiogenesis from a systems perspective. It is found that invasion percolation is better than diffusion limited aggregation at matching experimental data. We also present evidence that the distribution of the lengths of real tubule complexes follows a power law.

Ab initio multireference configuration-interaction theoretical study on the low-lying spin states in binuclear transition-metal complex: Magnetic exchange of [(NH3)5Cr(μ-OH)Cr(NH3)5]5+ and [Cl3FeOFeCl3]2−

The magnetic exchange interaction behavior and energy spectrum of low-lying spin states are investigated by using ab initio multireference configuration-interaction method for the representative binuclear transition-metal complexes [(NH(3))(5)Cr(mu-OH)Cr(NH(3))(5)](5+) and [Cl(3)FeOFeCl(3)](2-). Our calculations for the nonmodeling real title complexes found that under the appropriate basis sets and active space, ab initio method at multireference configuration-interaction level of theory is able to give accurate energy spectrum of low-lying spin states within reachable computation demand nowadays and the deviation of magnetic exchange interaction to Lande interval rule can be described by the biquadratic correction in terms of Heisenberg spin Hamiltonian. As a methodology comparison, density-functional theory combined with broken-symmetry approach provides an alternative yet efficient approach to produce accurate numerical results, but there are dependences on the particular chosen exchange-correlation functionals and system dependent. The spin population analyses at complete active space self-consistent-field level of the theory provide an instructively understanding and prediction for the magnetic interaction mechanism.

Ab initio quantum mechanical study of the binding energies of human estrogen receptor α with its ligands: An application of fragment molecular orbital method

We have theoretically examined the relative binding affinities (RBA) of typical ligands, 17beta-estradiol (EST), 17alpha-estradiol (ESTA), genistein (GEN), raloxifene (RAL), 4-hydroxytamoxifen (OHT), tamoxifen (TAM), clomifene (CLO), 4-hydroxyclomifene (OHC), diethylstilbestrol (DES), bisphenol A (BISA), and bisphenol F (BISF), to the alpha-subtype of the human estrogen receptor ligand-binding domain (hERalpha LBD), by calculating their binding energies. The ab initio fragment molecular orbital (FMO) method, which we have recently proposed for the calculations of macromolecules such as proteins, was applied at the HF/STO-3G level. The receptor protein was primarily modeled by 50 amino acid residues surrounding the ligand. The number of atoms in these model complexes is about 850, including hydrogen atoms. For the complexes with EST, RAL, OHT, and DES, the binding energies were calculated again with the entire ERalphaLBD consisting of 241 residues or about 4000 atoms. No significant difference was found in the calculated binding energies between the model and the real protein complexes. This indicates that the binding between the protein and its ligands is well characterized by the model protein with the 50 residues. The calculated binding energies relative to EST were very well correlated with the experimental RBA (the correlation coefficient r=0.837) for the ligands studied in this work. We also found that the charge transfer between ER and ligands is significant on ER-ligand binding. To our knowledge, this is the first achievement of ab initio quantum mechanical calculations of large molecules such as the entire ERalphaLBD protein.

Complexation of several fungicides with beta-cyclodextrin: determination of the association constants and isolation of the solid complexes.

The formation of inclusion complexes with beta-cyclodextrin was studied for several popular fungicides of different types: prochloraz, 2-phenylphenol, thiophanate methyl, 8-hydroxyquinoline, and benalaxyl. Phase solubility diagrams showed that in all cases complexation takes place, leading to an important increase of water solubility in prochloraz and benalaxyl. Equilibrium association constants could be determined from the phase solubility data and from NMR titrations in the case of 2-phenylphenol. Because of the low solubility of the complex formed between 8-hydroxyquinoline and beta-cyclodextrin, the corresponding association constant could not be determined. The solid complexes of fungicide-cyclodextrin were prepared and isolated by different methods. The isolation of real complexes and not physical mixtures was confirmed in the cases of prochloraz, 2-phenylphenol, and benalaxyl by differential scanning calorimetry.

Mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters catalyzed by BINAP-ruthenium(II) diacetate.

The mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters with Ru(CH(3)COO)(2)[(S)-binap] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), giving the S saturated products in >90% ee, has been investigated by means of a kinetic study, deuterium labeling experiments, isotope effect measurements, and NMR and X-ray analysis of certain Ru complexes. The hydrogenation in methanol under a low H2 pressure proceeds via a monohydride-unsaturate mechanism that involves the initial RuH formation followed by a reaction with an olefinic substrate. The migratory insertion in the enamide-RuH chelate complex occurs reversibly and endergonically in an exo manner, giving a five-membered metallacycle intermediate. The cleavage of the Ru-C bond is achieved with either H2 (major) or CH3OH (minor). Both of the pathways result in overall cis hydrogenation products. The hydrogen at C3 is mainly from an H2 molecule, and the C2 hydrogen is from another H2 or protic CH3OH. The major S and minor R enantiomers are produced via the same mechanism involving diastereomeric intermediates. The turnover rate is limited by the step of hydrogenolysis of a half-hydrogenated metallacyclic intermediate. The participation of two different hydrogen donor molecules is in contrast to the pairwise dihydrogenation using a single H2 molecule in the RhI-catalyzed reaction which occurs via a dihydride mechanism. In addition, the sense of asymmetric induction is opposite to that observed with S-BINAP-RhI catalysts. The origin of this phenomenon is interpreted in terms of stereocomplementary models of the enamide/metal chelate complexes. A series of model stoichiometric reactions mimicking the catalytic steps has indicated that most NMR-observable Ru complexes are not directly involved in the catalytic hydrogenation but are reservoirs of real catalytic complexes or even side products that retard the reaction.

Effect of the hydrophobic nature of triacetyl-beta-cyclodextrin on the complexation with nicardipine hydrochloride: physicochemical and dissolution properties of the kneaded and spray-dried complexes.

The inclusion ability of triacetyl-beta-cyclodextrin (TAbetaCD), a hydrophobic cyclodextrin (CD) derivative was examined, using nicardipine hydrochloride (NC) as model drug. The binary compounds were prepared in a 1 : 1 molar ratio by the kneading and the spray-drying techniques. In order to confirm the complexation between NC and TAbetaCD in the solid state, differential scanning calorimetry, X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscopy were carried out and the results were compared with the corresponding physical mixture in the same molar ratio. The kneaded product presented only slight modifications on the drug physicochemical and morphological properties, which could mean that no complex formation occurred during this process. In contrast, spray-drying was found to produce inclusion complexes with amorphous nature. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the United States Pharmacopoeia (USP) basket method. The NC in vitro release from the kneaded and spray-dried products was markedly retarded in both dissolution media. However, this retarding effect was significantly more evident for the spray-dried compound. It was concluded that the formation of real inclusion complexes could only be achieved by the spray-drying method.

Analysis of knowledge-based protein-ligand potentials using a self-consistent method.

We propose a self-consistent approach to analyze knowledge-based atom-atom potentials used to calculate protein-ligand binding energies. Ligands complexed to actual protein structures were first built using the SMoG growth procedure (DeWitte & Shakhnovich, 1996) with a chosen input potential. These model protein-ligand complexes were used to construct databases from which knowledge-based protein-ligand potentials were derived. We then tested several different modifications to such potentials and evaluated their performance on their ability to reconstruct the input potential using the statistical information available from a database composed of model complexes. Our data indicate that the most significant improvement resulted from properly accounting for the following key issues when estimating the reference state: (1) the presence of significant nonenergetic effects that influence the contact frequencies and (2) the presence of correlations in contact patterns due to chemical structure. The most successful procedure was applied to derive an atom-atom potential for real protein-ligand complexes. Despite the simplicity of the model (pairwise contact potential with a single interaction distance), the derived binding free energies showed a statistically significant correlation (approximately 0.65) with experimental binding scores for a diverse set of complexes.

Chromatographic Methods to Study Protein–Protein Interactions

Proteins and enzymes are now generally thought to be organized within the cell to form clusters in a dynamic and versatile way, and heterologous protein–protein interactions are believed to be involved in virtually all cellular events. Therefore we need appropriate tools to detect and study such interactions. Chromatographic techniques prove to be well suited for this kind of investigation. Real complexes formed between proteins can be studied by classic gel filtration. When enzymes are studied, active enzyme gel chromatography is a useful alternative. A variant of classic gel filtration is gel filtration equilibrium analysis, which is similar to equilibrium dialysis. When the association formed is only dynamic and equilibrates very rapidly, either the Hummel–Dryer method of equilibrium gel filtration or large-zone equilibrium filtration sometimes allows the interactions to be analyzed, both qualitatively and quantitatively. Very often, however, interactions between enzymes and proteins can only be evidenced in vitro in media that mimic the intracellular situation. Immobilized proteins are excellent tools for this type of research. Several examples are indeed known where the immobilization of an enzyme on a solid support does not affect its real properties, but rather changes its environment in such a way that the diffusion becomes limiting. Affinity chromatography using immobilized proteins allows the analysis of heterologous protein–protein interactions, both qualitatively and quantitatively. A useful alternative appears to be affinity electrophoresis. The latter technique, however, is exclusively qualitative. All these techniques are described and illustrated with examples taken from the literature.