Fragment Potential Research Articles

A Direct, Quantitative Connection between Molecular Dynamics Simulations and Vibrational Probe Line Shapes.

A quantitative connection between molecular dynamics simulations and vibrational spectroscopy of probe-labeled systems would enable direct translation of experimental data into structural and dynamical information. To constitute this connection, all-atom molecular dynamics (MD) simulations were performed for two SCN probe sites (solvent-exposed and buried) in a calmodulin-target peptide complex. Two frequency calculation approaches with substantial nonelectrostatic components, a quantum mechanics/molecular mechanics (QM/MM)-based technique and a solvatochromic fragment potential (SolEFP) approach, were used to simulate the infrared probe line shapes. While QM/MM results disagreed with experiment, SolEFP results matched experimental frequencies and line shapes and revealed the physical and dynamic bases for the observed spectroscopic behavior. The main determinant of the CN probe frequency is the exchange repulsion between the probe and its local structural neighbors, and there is a clear dynamic explanation for the relatively broad probe line shape observed at the "buried" probe site. This methodology should be widely applicable to vibrational probes in many environments.

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome

BackgroundGuidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. ObjectivesThis prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. MethodsA total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome–related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). ResultsOverall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. ConclusionsIn Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701)

Benchmarking the Effective Fragment Potential Dispersion Correction on the S22 Test Set.

The usual modeling of dispersion interactions in density functional theory (DFT) is often limited by the use of empirically fitted parameters. In this study, the accuracies of the popular empirical dispersion corrections and the first-principles derived effective fragment potential (EFP) dispersion correction are compared by computing the DFT-D and HF-D equilibria interaction energies and intermolecular distances of the S22 test set dimers. Functionals based on the local density approximation (LDA) and generalized gradient approximation (GGA), as well as hybrid functionals, are compared for the DFT-D calculations using coupled cluster CCSD(T) at the complete basis set (CBS) limit as the reference method. In general, the HF-D(EFP) method provides accurate equilibrium dimerization energies and intermolecular distances for hydrogen-bonded systems compared to the CCSD(T)/CBS reference data without using any empirical parameters. For dispersion-dominant and mixed systems, the structures and interaction energies obtained with the B3LYP-D(EFP) method are similar to or better than those obtained with the other DFT-D and HF-D methods. Overall, the first-principles derived -D(EFP) correction presents a robust alternative to the empirical -D corrections when used with the B3LYP functional for dispersion-dominant and mixed systems or with Hartree-Fock for hydrogen-bonded systems.

Dynamics of 17F + 58Ni reaction via complete and incomplete fusion processes at above barrier energies

The dynamics of 17F + 58Ni reaction induced via a loosely bound projectile (17F) is examined using the collective clusterization approach of the dynamical cluster decay model (DCM) with respect to the recent experimental data available at beam energies Ebeam=54.1 and 58.5 MeV. The calculations are done for quadrupole deformations of fragments using the optimum orientation approach. In view of the loosely bound nature of 17F, the main focus of the present work is on the comparison of complete and incomplete fusion. It is studied using various components such as fragmentation potential, mass distribution, and barrier modification. Different decay modes (ER, IMF, HMF, and fission) are also compared to determine the complete fusion and incomplete fusion paths. Additionally, the decay paths of the nucleus formed from loosely bound (17F) and tightly bound (16O) projectiles are compared. Furthermore, the role of temperature-dependent pairing strength is analyzed in terms of the binary fragmentation of the compound system formed.

Applicability of effective fragment potential version 2 – Molecular dynamics (EFP2-MD) simulations for predicting excess properties of mixed solvents

Effective fragment potential version 2 - molecular dynamics (EFP2-MD) simulations, where the EFP2 is a polarizable force field based on ab initio electronic structure calculations were applied to water-methanol binary mixture. Comparing EFP2s defined with (aug-)cc-pVXZ (X = D,T) basis sets, it was found that large sets are necessary to generate sufficiently accurate EFP2 for predicting mixture properties. It was shown that EFP2-MD could predict the excess molar volume. Since the computational cost of EFP2-MD are far less than ab initio MD, the results presented herein demonstrate that EFP2-MD is promising for predicting physicochemical properties of novel mixed solvents.

High affinity single-chain variable fragments are specific and versatile targeting motifs for extracellular vesicles.

Exosomes are extracellular vesicles that mediate cell-to-cell communication by transferring biological cargo, such as DNA, RNA and proteins. Through genetic engineering of exosome-producing cells or manipulation of purified exosomes, it is possible to load exosomes with therapeutic molecules and target them to specific cells via the display of targeting moieties on their surface. This provides an opportunity to exploit a naturally-occurring biological process for therapeutic purposes. In this study, we explored the potential of single chain variable fragments (scFv) as targeting domains to achieve delivery of exosomes to cells expressing a cognate antigen. We generated exosomes targeting the Her2 receptor and, by varying the affinity of the scFvs and the Her2 expression level on recipient cells, we determined that both a high-affinity anti-Her2-scFv (KD≤ 1 nM) and cells expressing a high level (≥106 copies per cell) of Her2 were optimally required to enable selective uptake. We also demonstrate that targeting exosomes to cells via a specific cell surface receptor can alter their intracellular trafficking route, providing opportunities to influence the efficiency of delivery and fate of intracellular cargo. These experiments provide solid data to support the wider application of exosomes displaying antibody fragments as vehicles for the targeted delivery of therapeutic molecules.

Design principles from multiscale simulations to predict nanostructure in self-assembling ionic liquids.

Molecular dynamics simulations (up to the nanoscale) were performed on the 3-methyl-1-pentylimidazolium ionic liquid cation paired with three anions; chloride, nitrate, and thiocyanate as aqueous mixtures, using the effective fragment potential (EFP) method, a computationally inexpensive way of modeling intermolecular interactions. The simulations provided insight (preferred geometries, radial distribution functions and theoretical proton NMR resonances) into the interactions within the ionic domain and are validated against 1H NMR spectroscopy and small- and wide-angle X-ray scattering experiments on 1-decyl-3-methylimidazolium. Ionic liquids containing thiocyanate typically resist gelation and form poorly ordered lamellar structures upon mixing with water. Conversely, chloride, a strongly coordinating anion, normally forms strong physical gels and produces well-ordered nanostructures adopting a variety of structural motifs over a very wide range of water compositions. Nitrate is intermediate in character, whereby upon dispersal in water it displays a range of viscosities and self-assembles into nanostructures with considerable variability in the fidelity of ordering and symmetry, as a function of water content in the binary mixtures. The observed changes in the macro and nanoscale characteristics were directly correlated to ionic domain structures and intermolecular interactions as theoretically predicted by the analysis of MD trajectories and calculated RDFs. Specifically, both chloride and nitrate are positioned in the plane of the cation. Anion to cation proximity is dependent on water content. Thiocyanate is more susceptible to water insertion into the second solvent shell. Experimental 1H NMR chemical shifts monitor the site-specific competition dependence with water content in the binary mixtures. Thiocyanate preferentially sits above and below the aromatic ring plane, a state disallowing interaction with the protons on the imidazolium ring.

Na+, F–, Br–, and Cl– Adsorptions and Penetrations on an Ice Surface

With the help of our quantum mechanical/effective fragment potential (QM/EFP) scheme, the adsorptions of Na+, F–, Br–, and Cl– ions on a hexagonal ice (0001) surface were theoretically studied. Drastically different adsorption behaviors depending upon ion signs and surface heterogeneity were observed. The positive Na+ ion forms 4–5 Na+–O interfacial bondings, regardless of the number of hydrogen dangling bonds (HDBs), yielding consistent adsorptions with large stabilization energies from −49.2 to −65.6 kcal/mol. On the other hand, the binding strengths of negative ions are sensitive to the number of HDBs. In the particular binding sites where there is no HDB, both Cl– and Br– cannot form a stable surface adsorption product. At the same binding site, more reactive F– can undergo insertion reaction into surface hydrogen bonding. A molecular HF and a hydroxide are formed on a site with one HDB, showing that the surface acid–base chemistry may depend upon the surface heterogeneity. In general, the versatile b...

Dispersion Interactions in QM/EFP.

The dispersion energy term between quantum-mechanical (QM) and classical (represented by effective fragment potentials, EFP) subsystems is developed and implemented. A new formulation is based on long-range perturbation theory and uses dynamic polarizability tensors of the effective fragments and electric field integrals and orbital energies of the quantum-mechanical subsystem. No parametrization is involved. The accuracy of the QM-EFP dispersion energy is tested on a number of model systems; the average mean unsigned error is 0.8 kcal/mol or 13% with respect to the symmetry adapted perturbation theory on the S22 data set of noncovalent interactions. The computational cost of the dispersion energy computation is low compared to the self-consistent field calculation of the QM subsystem. The dispersion energy is sensitive to the level of theory employed for the QM part and to the electrostatic interactions in the system. The latter means that the dispersion interactions in the QM/EFP method are not purely two-body but have more complex many-body behavior.

Dynamics of 47V* formed in 20Ne + 27Al reaction in view of fusion-fission and DIC mechanism

The decay mechanism of 47V* formed in direct kinematics (20Ne + 27Al is investigated within the collective clusterization approach of dynamical cluster decay model (DCM). All calculations are done for quadrupole (β 2i -deformed) choice of fragments by taking optimum orientations over a wide range of center of mass energies (E c. m. ∼ 83–125 MeV). According to the experimental evidence, there is a strong competition between fusion fission (FF) and deep inelastic collision (DIC) in the decay of 47V*, which are recognized as compound nucleus process and non-compound nucleus process, respectively. The decay cross sections of 47V* for both FF and DIC decay modes are addressed using DCM, and are found to be in agreement with the experimental data. It is important to mention that emitting fragments in both these decay channels maintain their homogeneity in terms of charge number, that lies in the region 3 ≤ Z ≤ 9. Hence, all possible isotopes contributing towards 3 ≤ Z ≤ 9 are taken into consideration here. Calculations of both FF and DIC are segregated on the basis of angular momentum windows, where 0 ≤ l ≤ l cr has been taken for FF and l cr < l ≤ l gr for DIC, as the later operates only due to the partial waves near grazing angular momentum. In DIC, preformation probability (P 0) is divided equally amongst the most favoured outgoing fragments. Moreover, the behavior of fragmentation potential, preformation probability, penetrability and emission time etc. is examined, in order to identify the most favorable isotopes contributing towards FF and DIC.

Spontaneous fission and competing ground state decay modes of actinide and transactinide nuclei

Based on the preformed cluster model, we have carried out a comprehensive theoretical study on the decay paths of ground state actinide and transactinide nuclei, specifically from $^{232}\mathrm{U}$ to $^{264}\mathrm{Hs}$ exhibiting the phenomenon of spontaneous fission (SF). This is an extension of our earlier studies on $\ensuremath{\alpha}$ decay, exotic cluster emission, and heavy particle radioactivity, where an effort is made to identify the most probable fragments in the SF process. These observations in turn, could provide a testing ground for future SF half-life measurements. To obtain a clear picture of the dynamics involved, the variations of fragmentation potential, preformation factor, and decay barrier height have been examined. The calculated potential energy surfaces show a change from a predominantly asymmetric fission to a symmetric fragmentation with the increase in the N/Z ratio of parent nuclei. In addition, an exclusive analysis of SF with $\ensuremath{\alpha}$ and other possible cluster emissions for the $^{232,234,236,238}\mathrm{U}$ parents was made to have better insight of nuclear structure information. In other words, the comparative nature of $\ensuremath{\alpha}$, cluster, heavy fragment, and SF decay paths is analyzed in view of shell closure property of the decay fragments. Interestingly, the calculated decay half-lives for the $^{82}\mathrm{Ge}$ heavy cluster are in fact shown to lie within the limits of experiments, thereby presenting themselves as exciting new possibilities which may be validated via future experiments.

Investigation of Ternary Fission of 98 252 Cf Using Three-Cluster and Unified Ternary Fission Models

Using three-cluster and unified ternary fission models, the ternary fission of 98252Cf is studied. We applied collinear and equatorial configurations to study the ternary fission of 98252Cf when the third fragment is 310Li. The nuclear potential energy in the three-cluster model and unified ternary fission model is calculated respectively, using Yukawa plus exponential and proximity formalisms. The relative yields of different fragmentation channels are calculated. Our results reveal that the ternary fragmentation potential of the three fragments and the relative yields depend on the configuration of three fragments and usedmodel. Two models predict that the lowest driving potential and highest relative yield take place for the fragment combination 51132Sb + 44110Ru + 310Li. Also, the values of driving potential and relative yield are not equal in the three-clustermodel and unified ternary fission model. For fragment combination 51132Sb + 44110Ru + 310Li, the relative yield based on the three-cluster model in collinear configuration is maximum, whereas the unified ternary fission model in equatorial configuration predicts the lowest relative yield.

Perivitelline threads associated with fragments in human cleavage stage embryos observed through time-lapse microscopy

Perivitelline threads (PVT) are defined as thin filaments that extend across the perivitelline space connecting the zona pellucida with the oolemma or, in some cases, blastomere membrane. This is the first report of PVT in human embryos. Time-lapse imagery from 525 blastocysts with either tested ploidy, known implantation status, or both, were reviewed for the presence of PVT, the cell stage when PVT were first observed, association with fragmentation, ploidy or implantation potential; PVT were observed in most embryos (404/525 [77%]). The euploidy rate was similar in embryos with PVT (61/152 [40%]) and without PVT (17/35 [49%]). Implantation rates were also similar in embryos with PVT (64/259 [25%]) and without PVT (25/90 [28%]). In the embryos in which PVT were observed, 98% (396/404) developed at the two-cell stage. In most embryos (384/404 [95%]), PVT were observed to directly pull fragments from the embryo. Fragmentation occurred significantly less frequently in embryos without PVT compared with PVT (81/121 [67%] versus 388/404 [96%]; P < 0.001). These data suggest an association between PVT and fragmentation. This study is limited in that PVT were not characterized so their nature and origin remain unknown and to be determined in future studies.

A study of probable alpha-ternary fission fragments of 257Fm

The probable α-accompanied cold ternary fission fragments of 257Fm are studied using six types of nuclear proximity potentials. We have studied the driving potential, probability, relative yield and half-lives of possible alpha ternary fission fragments. It is clear from present study that the alpha accompanied cold ternary fission reactions of 257Fm having minimum driving potential, maximum fission yield and small fission half lives for 48Ca + 205Pt + 4He. Hence this combination is recognized as most probable alpha ternary fission fragments of 257Fm due to the presence of doubly magic nucleus 48Ca. This study finds important in the experiments on alpha ternary fission of 257Fm.

Feature extraction based on time-singularity multifractal spectrum distribution in intracardiac atrial fibrillation signals

Non-linear analysis of electrograms (EGM) has been proposed as a tool to detect critical conduction sites (e.g., rotors vortex, multiple wavefronts) in atrial fibrillation (AF). Likewise, studies have shown that multifractal analysis is useful to detect critical activity in EGM signals. However, the multifractal spectrum does not consider the temporal information. There is a new mathematical formalism to overcome this limitation: the time-singularity multifractal spectrum distribution (TS-MFSD), which involves the time variation of the spectrum. In this manuscript, we describe the methodology to compute the TS-MFSD from EGM signals. Moreover, we propose a methodology to extract features from time-singularity spectrum and from singularity energy spectrum (SES). We tested the features in an EGM database labeled by experts as: non-fragmented, discrete fragmented potentials, disorganized activity, and continuous activity. We tested the area under the receiver operating characteristic (ROC) curve. The proposed features achieve an area under the ROC curve of 95.17% when detecting signals with continuous activity. These results outperform those reported using multifractal analysis. To our knowledge, this is the first work that report the use of TS-MFSD in biomedical signals and our findings suggest that time-singularity has the potential to be used in the study of non-stationary behavior of EGM signals in AF.

Effect of solvation on the ionization of guanine nucleotide: A hybrid QM/EFP study.

Ionization of nucleobases is affected by their biological environment, which includes both the effect of adjacent nucleotides as well as the presence of water around it. Guanine and its nucleotide have the lowest ionization potentials among the various DNA bases. Therefore, the threshold of ionization is dependent on that of guanine and its characterization is crucial to the prediction of interaction of light with DNA. We investigate the effect of solvation on the vertical ionization energies (VIEs) of guanine and its nucleotide. In this work, we have used hybrid quantum mechanics/molecular mechanics (QM/MM) approach with effective fragment potential as the MM method of choice and equation-of-motion coupled-cluster for ionization potential with singles and doubles (EOM-IP-CCSD) as the QM method. The performance of the hybrid scheme with respect to the full QM method shows an accuracy of ≤ 0.02-0.04 eV. The lowest few ionizations of the nucleotide are found to be from different parts of the moiety, that is, the nucleic acid base, phosphate, or sugar, and these ionization energies are very closely spaced giving rise to a very complicated spectrum. Furthermore, microsolvation has large effects on these ionizations and can lead to red or blue shift depending on the position of the water molecule. Even a single water molecule can change the order of ionized states in the nucleotide. The VIEs of the bulk solvated chromophores are predicted and compared to existing experimental spectra. The predominant role of polarization in the solvatochromic shift is noticed. © 2017 Wiley Periodicals, Inc.

Intramolecularly Coordinated 2‐Iminomethylphenyltellurium Compounds

Procedures for the synthesis of 2‐(tBuNCH)C6H4Te(S2CNEt2) (1a), 2‐(2′,6′‐iPr2C6H3NCH)C6H4Te(S2CNEt2) (1b), [2‐(tBuNCH)C6H4]2Te (2a), 2‐(tBuNCH)C6H4TeCl (3a), and 2‐(tBuNCH)C6H4TeCl3 (4a) have been developed. Compounds 1a–4a possess 2‐iminomethylphenyl groups that provide intramolecular N donation to the Te atoms, which was investigated by multinuclear NMR spectroscopy and X‐ray crystallography. The Te–N bond lengths increase in the order 3a [2.203(2) Å] &lt; 4a [2.286(1) Å] &lt; 1b [2.337(2) Å] &lt; 1a [2.407(2) Å] &lt; 2a [2.688(2) Å]. The nature of these bonds, which span a wide range from weak to strongly dative, was computationally analyzed for 1a–4a by means of DFT calculations using real‐space bonding indicators derived from the atoms‐in‐molecules (AIM), electron localizability indicator (ELI‐D), and noncovalent interactions (NCI) indicator toolkits. The analysis of the electrostatic potentials (ESPs) of proper fragments revealed considerable σ‐hole bond contributions in 3 and 4.

Coupled-cluster based approach for core-level states in condensed phase: Theory and application to different protonated forms of aqueous glycine.

A theoretical approach for calculating core-level states in condensed phase is presented. The approach is based on the equation-of-motion coupled-cluster (EOM-CC) theory and effective fragment potential (EFP) method. By introducing approximate treatment of double excitations in the EOM-CC with single and double substitutions ansatz, we address poor convergence issues that are encountered for the core-level states and significantly reduce computational costs. While the approximations introduce relatively large errors in the absolute values of transition energies, the errors are systematic. Consequently, chemical shifts, changes in ionization energies relative to reference systems, are reproduced reasonably well. By using different protonation forms of solvated glycine as a benchmark system, we show that our protocol is capable of reproducing the experimental chemical shifts with a quantitative accuracy. The results demonstrate that chemical shifts are very sensitive to the solvent interactions and that explicit treatment of a solvent, such as within EFP framework, is essential for achieving quantitative accuracy.

Effective Fragment Potential Method for H-Bonding: How To Obtain Parameters for Nonrigid Fragments.

Accuracy of the effective fragment potential (EFP) method was explored for describing intermolecular interaction energies in three dimers with strong H-bonded interactions, formic acid, formamide, and formamidine dimers, which are a part of HBC6 database of noncovalent interactions. Monomer geometries in these dimers change significantly as a function of intermonomer separation. Several EFP schemes were considered, in which fragment parameters were prepared for a fragment in its gas-phase geometry or recomputed for each unique fragment geometry. Additionally, a scheme in which gas-phase fragment parameters are shifted according to relaxed fragment geometries is introduced and tested. EFP data are compared against the coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) method in a complete basis set (CBS) and the symmetry adapted perturbation theory (SAPT). All considered EFP schemes provide a good agreement with CCSD(T)/CBS for binding energies at equilibrium separations, with discrepancies not exceeding 2 kcal/mol. However, only the schemes that utilize relaxed fragment geometries remain qualitatively correct at shorter than equilibrium intermolecular distances. The EFP scheme with shifted parameters behaves quantitatively similar to the scheme in which parameters are recomputed for each monomer geometry and thus is recommended as a computationally efficient approach for large-scale EFP simulations of flexible systems.

Multi-residue determination of organochlorine pesticides in vegetables in Kirklareli, Turkey by gas chromatography–mass spectrometry

The aim of this study was to investigate the level of organochlorine pesticides use for treatment of tomatoes, eggplants and cucumbers in Kirklareli, Turkey. Eighteen organochlorine pesticides were identified in vegetable samples using microwave or Soxhlet extraction, and results were obtained by gas chromatography–mass spectrometry. The optimized conditions were 1 mL/min for flow rate in the mobile phase, 1 μL for injection volume and 70 V for fragmentation potential. The analytical parameters show that the microwave oven extraction procedure provided the best results when compared to the Soxhlet extraction procedure. Samples were prepared for analysis with hexane‒dichlormethane (1: 1, v/v, 40 mL) using a solid-phase extraction method. The limits of detection and quantitation for the eighteen analytes were between 0.02–0.26 and 0.06–0.87 μg/L, respectively, and the relative standard deviations of the migration time ranged from 2.4 to 8.9%. The recoveries of surrogate spiked in vegetable samples ranged from 70 to 116%, respectively. The obtained concentrations of pesticides in all vegetables studied were proved in the range of ND–123 μg/kg. The organochlorine pesticide sum was below the legal limit, except for Endrin and Methoxychlor, which requires a further elucidation of the organochlorine pesticides pollution sources in the region. These studies on accumulation of organochlorine pesticides were necessary for accomplishing a comprehensive ecological risk assessment.