The one-dimensional model of Hann et al. (J Chem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzmann distribution has been used to calculate the probability of measuring the sensitivity of the interactions as the asymptotic limits of the distribution better describe the behavior of the interactions under experimental conditions. Based on our model, we hypothesized that molecules of lower complexity are preferred for target based screening campaigns, while augmenting such a library with moieties of moderate complexities maybe better suited for phenotypic screens. The validity of the hypothesis has been assessed via the analysis of the hit rate profiles for four ChemBL datasets for enzymatic and phenotypic screens. 相似文献
Spontaneous melting of a perfect crystalline graphene model in 2D space is studied via molecular dynamics simulation. Model containing 104 atoms interacted via long-range bond-order potential (LCBOP) is heated up from 50 to 8,450 K in order to see evolution of various thermodynamic quantities, structural characteristics and occurrence of various structural defects. We find that spontaneous melting of our graphene model in 2D space exhibits a first-order behaviour of the transition from solid 2D graphene sheet into a ring-like structure 2D liquid. Occurrence and clustering of Stone–Wales defects are the first step of melting process followed by breaking of C–C bonds, occurrence/growth of various types of vacancies and multi-membered rings. Unlike that found for melting of a 2D crystal with an isotropic bonding, these defects do not occur homogeneously throughout the system, they have a tendency to aggregate into a region and liquid phase initiates/grows from this region via tearing-like or crack-propagation-like mechanism. Spontaneous melting point of our graphene model occurs at Tm = 7,750 K. The validity of classical nucleation theory and Berezinsky–Kosterlitz–Thouless–Nelson–Halperin–Young (BKTNHY) one for the spontaneous melting of our graphene model in strictly 2D space is discussed. 相似文献
In this study, GaAs metal–oxide–semiconductor (MOS) capacitors using Y‐incorporated TaON as gate dielectric have been investigated. Experimental results show that the sample with a Y/(Y + Ta) atomic ratio of 27.6% exhibits the best device characteristics: high k value (22.9), low interfacestate density (9.0 × 1011 cm–2 eV–1), small flatband voltage (1.05 V), small frequency dispersion and low gate leakage current (1.3 × 10–5A/cm2 at Vfb + 1 V). These merits should be attributed to the complementary properties of Y2O3 and Ta2O5:Y can effectively passivate the large amount of oxygen vacancies in Ta2O5, while the positively‐charged oxygen vacancies in Ta2O5 are capable of neutralizing the effects of the negative oxide charges in Y2O3. This work demonstrates that an appropriate doping of Y content in TaON gate dielectric can effectively improve the electrical performance for GaAs MOS devices.
Capacitance–voltage characteristic of the GaAs MOS capacitor with TaYON gate dielectric (Y content = 27.6%) proposed in this work with the cross sectional structure and dielectric surface morphology as insets. 相似文献
Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug-resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced. Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP-site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR. 相似文献
Structurally robust tetradentate gold(III)-emitters have potent material applications but are rare and unprecedented for those displaying thermally activated delayed fluorescence (TADF). Herein, a novel synthetic route leading to the preparation of highly emissive, charge-neutral tetradentate [C^C^N^C] gold(III) complexes with 5-5-6-membered chelate rings has been developed through microwave-assisted C−H bond activation. These complexes show high thermal stability and with emission origin (3IL, 3ILCT, and TADF) tuned by varying the substituents of the C^C^N^C ligand. With phenoxazine/diphenylamine substituent, we prepared the first tetradentate gold(III) complexes that are TADF emitters with emission quantum yields of up to 94 % and emission lifetimes of down to 0.62 μs in deoxygenated toluene. These tetradentate AuIII TADF emitters showed good performance in vacuum-deposited OLEDs with maximum EQEs of up to 25 % and LT95 of up to 5280 h at 100 cd m−2. 相似文献
Materials exhibiting excitation wavelength‐dependent photoluminescence (Ex‐De PL) in the visible region have potential applications in bioimaging, optoelectronics and anti‐counterfeiting. Two multifunctional, chiral [Au(NHC)2][Au(CN)2] (NHC=(4R,5R)/(4S,5S)‐1,3‐dimethyl‐4,5‐diphenyl‐4,5‐dihydro‐imidazolin‐2‐ylidene) complex double salts display Ex‐De circularly polarized luminescence (CPL) in doped polymer films and in ground powder. Emission maxima can be dynamically tuned from 440 to 530 nm by changing the excitation wavelength. The continuously tunable photoluminescence is proposed to originate from multiple emissive excited states as a result of the existence of varied AuI???AuI distances in ground state. The steric properties of the NHC ligand are crucial to the tuning of AuI???AuI distances. An anti‐counterfeiting application using these two salts is demonstrated. 相似文献
This article describes the roadside traffic noise surveys conducted in heavily built-up urban areas in Hong Kong. Noise measurements were carried out along 18 major roads in 1999. The measurement data included L10, L50, L90, Leq, Lmax, the number of light vehicles, the number of heavy vehicles, the total traffic flow, and the average speed of vehicles. Statistical analysis using the analysis of variance (ANOVA) and Tukey test (p<0.05) reveals that the total traffic flow and the number of heavy vehicles are the most significant factors of urban traffic noise. Multiple regression was used to derive a set of empirical formulas for predicting L10 noise level due to road traffic. The accuracy of these empirical formulas is quantified and compared to that of another widely used prediction model in Hong Kong--the Calculation of Road Traffic Noise. The applicability of the selected multiple regression model is validated by the noise measurements performed in the winter of 2000. 相似文献
We compute the curvature of the -metric on the direct image of a family of Hermitian holomorphic vector bundles over a family of compact Kähler manifolds. As an application, we show that the -metric on the direct image of a family of ample line bundles over a family of abelian varieties and equipped with a family of canonical Hermitian metrics is always projectively flat. When the parameter space is a compact Kähler manifold, this leads to the poly-stability of the direct image with respect to any Kähler form on the parameter space.