Statistical potential for modeling and ranking of protein-ligand interactions

Applications in structural biology and medicinal chemistry require protein-ligand scoring functions for two distinct tasks: (i) ranking different poses of a small molecule in a protein binding site and (ii) ranking different small molecules by their complementarity to a protein site. Using probability theory, we developed two atomic distance-dependent statistical scoring functions: PoseScore was optimized for recognizing native binding geometries of ligands from other poses and RankScore was optimized for distinguishing ligands from nonbinding molecules. Both scores are based on a set of 8,885 crystallographic structures of protein-ligand complexes but differ in the values of three key parameters. Factors influencing the accuracy of scoring were investigated, including the maximal atomic distance and non-native ligand geometries used for scoring, as well as the use of protein models instead of crystallographic structures for training and testing the scoring function. For the test set of 19 targets, RankScore improved the ligand enrichment (logAUC) and early enrichment (EF(1)) scores computed by DOCK 3.6 for 13 and 14 targets, respectively. In addition, RankScore performed better at rescoring than each of seven other scoring functions tested. Accepting both the crystal structure and decoy geometries with all-atom root-mean-square errors of up to 2 ? from the crystal structure as correct binding poses, PoseScore gave the best score to a correct binding pose among 100 decoys for 88% of all cases in a benchmark set containing 100 protein-ligand complexes. PoseScore accuracy is comparable to that of DrugScore(CSD) and ITScore/SE and superior to 12 other tested scoring functions. Therefore, RankScore can facilitate ligand discovery, by ranking complexes of the target with different small molecules; PoseScore can be used for protein-ligand complex structure prediction, by ranking different conformations of a given protein-ligand pair. The statistical potentials are available through the Integrative Modeling Platform (IMP) software package (http://salilab.org/imp) and the LigScore Web server (http://salilab.org/ligscore/).     

Structural characterization of flavonol 3,7-di-O-glycosides and determination of the glycosylation position by using negative ion electrospray ionization tandem mass spectrometry

Flavonol 3,7-di-O-glycosides were investigated by negative ion electrospray ionization tandem mass spectrometry using a quadrupole linear ion trap (LIT) mass spectrometer. The results indicate that the fragmentation behavior of flavonol 3,7-di-O-glycosides is substantially different from that of their isomeric mono-O-diglycosides. In order to characterize a flavonoid as a flavonol 3,7-di-O-glycoside, both [Y3(0) - H]-* and [Y(0) - 2H]- ions should be present in [M - H]- product ion spectrum. The MS(3) product ion spectra of Y3(0)-, [Y3(0) - H]-* and Y7(0)- ions generated from the [M - H]- ion provide sufficient structural information for the determination of glycosylation position. Furthermore, the glycosylation positions are determined by comparing the relative abundances of Y3(0)- and Y7(0)- ions and their specific fragmentation patterns with those of flavonol mono-O-glycosides. In addition, a [Y3(0) - H]-* ion formed by the homolytic cleavage of 3-O glycosidic bond with high abundance points to 3-O glycosylation, while a [Y(0) - 2H]- ion formed by the elimination of the two sugar residues is consistent with glycosylation at both the 3-O and 7-O positions. Investigation of negative ion ESI-MS(2) and MS(3) spectra of flavonol O-glycosides allows their rapid characterization as flavonol 3,7-di-O-glycoside and their differentiation from isomeric mono-O-diglycosides, and also enables their direct analysis in crude plant extracts.     

含有异噁唑的S-三唑[3,4-b]-1,3,4-噻二嗪、咪唑[2,1-b]-1,3,4-噻二唑和咪唑[2,1-b]-1,3,4-噁二唑衍生物的合成

异噁唑衍生物作为一类重要的生物活性物质,其合成一直受到人们的关注,其中德国HMR公司开发研制的新型抗内风湿性关节炎药来氟米特(Leftunomide)已于1998年在美国率先上市,该药还具有很好的免疫调节作用．7H-均三唑[3,4-b]-1,3,4-噻二嗪、咪唑并[2,1-b]噻唑和咪唑并[2,1-b]-1,3,4-噻二唑衍生物均表现出广谱的生物活性．     

乙醇-无机盐双水体系中研究XO的萃取行为

研究了二甲酚橙(XO)在乙醇-无机盐双水相萃取体系中的萃取行为,对无机盐种类、缓冲溶液和其用量等条件进行了优化,在最优条件下研究了上下层体积与萃取率、分配比等因素的变化规律.结果表明:在使用K2HPO4 - KH2PO4缓冲溶液5.0 mL,95％乙醇6.0 mL,K2HPO46.0g,乙醇和蒸馏水体积比为1∶2的条件...     

Interferometric measurement of the atomic dipole phase for the two electronic quantum paths generating high-order harmonics

The first direct measurement of the atomic dipole phase in high-order harmonic generation obtained by an interferometric technique in the extreme ultraviolet (XUV) is reported. The effects associated with both the main quantum paths involved in the emission of a given plateau harmonic are investigated and compared with the expectations of the semi-classical model, which offers a very simple physical picture for the understanding of the involved electronic dynamics.     

Attosecond resolved electron release in two-color near-threshold photoionization of N2

We have simulated two-color photoionization of N(2) by solving the time-dependent Schr?dinger equation with a simple model accounting for the correlated vibronic dynamics of the molecule and of the ion N(2)(+). Our results, in very good agreement with recent experiments [Haessler et al., Phys. Rev. A 80, 011404 (2009)], show how a resonance embedded in the molecular continuum dramatically affects the phases of the two-photon transition amplitudes. In addition, we introduce a formal relation between these measurable phases and the photoelectron release time, opening the way to attosecond time-resolved measurements, equivalent to double-slit experiments in the time domain.     

Effect of doping on structural,optical and electrical properties of nanostructure ZnO films deposited onto a-Si:H/Si heterojunction

We investigated the structural; optical and electrical properties of ZnO thin films as the n-type semiconductor for silicon a-Si:H/Si heterojunction photodiodes. The ZnO film forms the front contact of the super-strata solar cell and has to exhibit good electrical (high conductivity) and optical (high transmittance) properties. In this paper we focused our attention on the influence of doping on device performance. The results show that the X-ray diffraction (XRD) spectra revealed a preferred orientation of the crystallites along c-axis. SEM images show that all films display a granular, polycrystalline morphology and the ZnO:Al exhibits a better grain uniformity. The transmittance of the doped films was found to be higher when compared to undoped ZnO. A low resistivity of the order of 2.8 × 10⁻⁴ Ω cm is obtained for ZnO:Al using 0.4 M concentration of zinc acetate. The photoluminescence (PL) spectra exhibit a blue band with two peaks centered at 442 nm (2.80 eV) and 490 nm (2.53 eV). It is noted that after doping the ZnO films a shift of the band by 22 nm (0.15 eV) is recorded and a high luminescence occurs when using Al as a dopant. Dark I–V curves of ZnO/a-Si:H/Si structure showed large difference, which means there is a kind of barrier to current flow between ZnO and a-Si:H layer. Doping films was applied and the turn-on voltages are around 0.6 V. Under reverse bias, the current of the ZnO/a-Si:H/Si heterojunction is larger than that of ZnO:Al/a-Si:H/Si. The improvement with ZnO:Al is attributed to a higher number of generated carriers in the nanostructure (due to the higher transmittance and a higher luminescence) that increases the probability of collisions.     

Extreme ultraviolet interferometry measurements with high-order harmonics

We demonstrate that high-order harmonics generated by short, intense laser pulses in gases provide an interesting radiation source for extreme ultraviolet interferometry, since they are tunable, coherent, of short pulse duration, and simple to manipulate. Harmonics from the 9th to the 15th are used to measure the thickness of an aluminum layer. The 11th harmonic is used to determine the spatial distribution of the electron density of a plasma produced by a 300-ps laser. Electronic densities higher than 2-10(20)electrons/cm>(3) are measured.     

Optimization of attosecond pulse generation

The generation of attosecond pulses by superposition of high harmonics relies on their synchronization in the emission. Our experiments in the low-order, plateau, and cutoff regions of the spectrum reveal different regimes in the electron dynamics determining the synchronization quality. The shortest pulses are obtained by combining a spectral filtering of harmonics from the end of the plateau and the cutoff, and a far-field spatial filtering that selects a single electron quantum path contribution to the emission. This method applies to isolated pulses as well as pulse trains.