The SQM/COSMO filter: reliable native pose identification based on the quantum-mechanical description of protein–ligand interactions and implicit COSMO solvation

Current virtual screening tools are fast, but reliable scoring is elusive. Here, we present the "SQM/COSMO filter", a novel scoring function featuring a quantitative semiempirical quantum mechanical (SQM) description of all types of noncovalent interactions coupled with implicit COSMO solvation. We show unequivocally that it outperforms eight widely used scoring functions. The accuracy and chemical generality of the SQM/COSMO filter make it a perfect tool for late stages of virtual screening

Multi MeV protons, deuterons and carbon ions produced by the PALS laser system

Multi MeV ions and fusion neutrons were generated by focused radiation of the 3 TW Prague Asterix Laser System (PALS). The use of 8 μm Al foil as XUV filter positioned in front of an ion collector allowed measuring currents of 4-MeV protons emitted behind a thin target in the forward direction. The proton energy of 4 MeV generated by a PALS laser irradiance Iλ2~5×1016 W cm-2 μm2 on target is nominally reachable for picosecond lasers when they deliver the intensity Iλ2~3×1018 W cm-2 μm2. The enhanced maximum proton energy is favoured by a non-linear interaction of the laser beam with the pre-generated plasma. Nonlinear processes also cause enhancement in the yield of fusion neutrons per focused laser energy from the CD2 plasma. The obtained results show that an equivalent neutron yield was reached by ps- and sub-ps laser beams for Iλ2~1019 W cm-2 μm2. The hampering influence of the electromagnetic pulse generated within the interaction chamber on diagnostics signals was eliminated

Efficient Neutron Production from a Novel Configuration of Deuterium Gas-Puff Z-Pinch

A novel configuration of a deuterium z pinch has been used to generate fusion neutrons. Injecting an outer hollow cylindrical plasma shell around an inner deuterium gas puff, neutron yields from DD reactions reached Y-n = (2.9 +/- 0.3) x 10(12) at 700 ns implosion time and 2.7 MA current. Such a neutron yield means a tenfold increase in comparison with previous deuterium gas puff experiments at the same current generator. The increase of beam-target yields was obtained by a larger amount of current assembled on the z-pinch axis, and subsequently by higher induced voltage and higher energies of deuterons. A stack of CR-39 track detectors on the z-pinch axis showed hydrogen ions up to 38 MeV. Maximum neutron energies of 15 and 22 MeV were observed by radial and axial time-of-flight detectors, respectively. The number of DD neutrons per one joule of stored plasma energy approached 5 x 10(7). This implies that deuterium gas puff z pinches belong to the most efficient plasma-based sources of DD neutrons

A neuroscientific evaluation of driver rehabilitation:Functional neuroimaging demonstrates the effectiveness of empathy induction in altering brain responses during social information processing

An alarming number of traffic-related deaths occur each year on European roads alone. Figures reveal that the vast majority of road-traffic accidents are caused by drivers themselves, and so further improvements in road safety require developments in driver training and rehabilitation. This study evaluated a novel approach to driver rehabilitation-specifically, empathy induction as a means of changing attitudes towards risky driving. To assess the effectiveness of this method, the present study employed functional magnetic resonance imaging (fMRI) to compare brain function before and after a short program of empathy induction in 27 drivers whose licenses had been revoked after serious traffic offences (rehabilitated drivers [RDs]). In an extension of our previous research, we first assessed whether neural responses to empathy-eliciting social stimuli changed in these RDs. In order to isolate the neurophysiological effects of empathy induction from any other potential influences, we compared these RDs to a sample of 27 age-, handedness- and driving experience-matched control drivers (CDs) who had no exposure to the program. We then performed dual-fMRI "hyperscanning" to evaluate whether empathy induction changed brain responses during real-world social interactions among drivers; namely, during co-operative and/or competitive exchanges. Our data reveal that RDs exhibited weaker brain responses to socio-emotional stimuli compared with CDs prior to the program, but this difference was reversed after empathy induction. Moreover, we observed differences between pre- and post-program assessments in patterns of brain responses in RDs elicited during competitive social exchanges, which we interpret to reflect a change in their proclivity to react to the perceived wrong-doing of other road users. Together, these findings suggest that empathy induction is an effective form of driver rehabilitation, and the utility of neuroscientific techniques for evaluating and improving rehabilitation programs

Semiconductor Detectors for Observation of Multi-MeV Protons and Ions Produced by Lasers

The application of time-of-flight Faraday cups and SiC detectors for the measurement of currents of fast ions emitted by laser-produced plasmas is reported. Presented analysis of signals of ion detectors reflects the design and construction of the detector used. A similarity relation between output signals of ion collectors and semiconductor detectors is established. Optimization of the diagnostic system is discussed with respect to the emission time of electromagnetic pulses interfering with signals induced by the fastest ions accelerated up to velocities of 107 m/s. The experimental campaign on laser-driven ion acceleration was performed at the PALS facility in Prague

Noncovalent Interactions by QMC: Speedup by One-Particle Basis-Set Size Reduction

While it is empirically accepted that the fixed-node diffusion Monte-Carlo (FN-DMC) depends only weakly on the size of the one-particle basis sets used to expand its guiding functions, limits of this observation are not settled yet. Our recent work indicates that under the FN error cancellation conditions, augmented triple zeta basis sets are sufficient to achieve a benchmark level of 0.1 kcal/mol in a number of small noncovalent complexes. Here we report on a possibility of truncation of the one-particle basis sets used in FN-DMC guiding functions that has no visible effect on the accuracy of the production FN-DMC energy differences. The proposed scheme leads to no significant increase in the local energy variance, indicating that the total CPU cost of large-scale benchmark noncovalent interaction energy FN-DMC calculations may be reduced.Comment: ACS book chapter, accepte

S66: A Well-balanced Database of Benchmark Interaction Energies Relevant to Biomolecular Structures

With numerous new quantum chemistry methods being developed in recent years and the promise of even more new methods to be developed in the near future, it is clearly critical that highly accurate, well-balanced, reference data for many different atomic and molecular properties be available for the parametrization and validation of these methods. One area of research that is of particular importance in many areas of chemistry, biology, and material science is the study of noncovalent interactions. Because these interactions are often strongly influenced by correlation effects, it is necessary to use computationally expensive high-order wave function methods to describe them accurately. Here, we present a large new database of interaction energies calculated using an accurate CCSD(T)/CBS scheme. Data are presented for 66 molecular complexes, at their reference equilibrium geometries and at 8 points systematically exploring their dissociation curves; in total, the database contains 594 points: 66 at equilibrium geometries, and 528 in dissociation curves. The data set is designed to cover the most common types of noncovalent interactions in biomolecules, while keeping a balanced representation of dispersion and electrostatic contributions. The data set is therefore well suited for testing and development of methods applicable to bioorganic systems. In addition to the benchmark CCSD(T) results, we also provide decompositions of the interaction energies by means of DFT-SAPT calculations. The data set was used to test several correlated QM methods, including those parametrized specifically for noncovalent interactions. Among these, the SCS-MI-CCSD method outperforms all other tested methods, with a root-mean-square error of 0.08 kcal/mol for the S66 data set

Accurate Treatment of Large Supramolecular Complexes by Double-Hybrid Density Functionals Coupled with Nonlocal van der Waals Corrections

In this work, we present a thorough assessment of the performance of some representative double-hybrid density functionals (revPBE0-DH-NL and B2PLYP-NL) as well as their parent hybrid and GGA counterparts, in combination with the most modern version of the nonlocal (NL) van der Waals correction to describe very large weakly interacting molecular systems dominated by noncovalent interactions. Prior to the assessment, an accurate and homogeneous set of reference interaction energies was computed for the supramolecular complexes constituting the L7 and S12L data sets by using the novel, precise, and efficient DLPNO-CCSD(T) method at the complete basis set limit (CBS). The correction of the basis set superposition error and the inclusion of the deformation energies (for the S12L set) have been crucial for obtaining precise DLPNO-CCSD(T)/CBS interaction energies. Among the density functionals evaluated, the double-hybrid revPBE0-DH-NL and B2PLYP-NL with the three-body dispersion correction provide remarkably accurate association energies very close to the chemical accuracy. Overall, the NL van der Waals approach combined with proper density functionals can be seen as an accurate and affordable computational tool for the modeling of large weakly bonded supramolecular systems.Financial support by the “Ministerio de Economía y Competitividad” (MINECO) of Spain and European FEDER funds through projects CTQ2011-27253 and CTQ2012-31914 is acknowledged. The support of the Generalitat Valenciana (Prometeo/2012/053) is also acknowledged. J.A. thanks the EU for the FP7-PEOPLE-2012-IEF-329513 grant. J.C. acknowledges the “Ministerio de Educación, Cultura y Deporte” (MECD) of Spain for a predoctoral FPU grant

Redox-dependent control of i-Motif DNA structure using copper cations

Previous computational studies have shown that Cu+ can act as a substitute for H+ to support formation of cytosine (C) dimers with similar conformation to the hemi-protonated base pair found in i-motif DNA. Through a range of biophysical methods, we provide experimental evidence to support the hypothesis that Cu+ can mediate C–C base pairing in i-motif DNA and preserve i-motif structure. These effects can be reversed using a metal chelator, or exposure to ambient oxygen in the air that drives oxidation of Cu+ to Cu2+, a comparatively weak ligand. Herein, we present a dynamic and redox-sensitive system for conformational control of an i-motif forming DNA sequence in response to copper cations

Plasticity in Major Ampullate Silk Production in Relation to Spider Phylogeny and Ecology

Spider major ampullate silk is a high-performance biomaterial that has received much attention. However, most studies ignore plasticity in silk properties. A better understanding of silk plasticity could clarify the relative importance of chemical composition versus processing of silk dope for silk properties. It could also provide insight into how control of silk properties relates to spider ecology and silk uses