The computer program LUDI: A new method for the de novo design of enzyme inhibitors

Summary A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates interaction sites, which are discrete positions in space suitable to form hydrogen bonds or to fill a hydrophobic pocket. The interaction sites are derived from distributions of nonbonded contacts generated by a search through the Cambridge Structural Database. An alternative route to generate the interaction sites is the use of rules. The second step is the fit of molecular fragments onto the interaction sites. Currently we use a library of 600 fragments for the fitting. The final step in the present program is the connection of some or all of the fitted fragments to a single molecule. This is done by bridge fragments. Applications are presented for the crystal packing of benzoic acid and the enzymes dihydrofolate reductase and trypsin.     

Improvement on peak-to-trough ratio of sampled fiber Bragg gratings with multiple phase shifts

Via a cascaded structure, the peak-to-trough ratio is considerably improved for sampled fiber Bragg gratings （SFBGs） based on multiple-phase-shift （MPS） technique. This cascaded filter is composed of two identical SFBGs which are inserted with the increasing or decreasing arrangement of phase shifts. With this inverse arrangement of MPS in grating design, the phase fluctuation of individual SFBG can be compensated, and as a result an excellent phase matching condition is realized. In this way, the peak-to- trough ratio in reflection spectra is improved from 6 to 12 dB when multiplication factor m = 4, and from 5dBto 10dBwhenm=8.     

电流镜及其在多值I2L电路开关级设计中的应用

运用开关信号理论和有界算术运算理论，对电流镜的多种性质进行了讨论，并系统研究了利用电流镜实现电流信号的各种算术运算，其中倍除运算属于初次提出，最后通过N进制半加电路和N值比较电路等两个设计实例介绍了电流镜技术在I^2L电路开关级设计中的应用。     

汽车覆盖件工艺补充面参数化设计方法

工艺补充面设计的合理性,是保证覆盖件成形质量的重要条件。工艺补充曲面设计和修改的便利性,是提高设计效率的重要途径。本文提出了建立可修改特征参数的截面线类型库,用双向NURBS蒙皮法分片生成工艺补充面的方法和流程,开发了相应的参数化设计模块。在此基础上可以快速实现基于用户控制的工艺补充面的参数化设计和修改。通过对汽车某些零件等实际覆盖件生成工艺补充面的数值仿真验证了可行性。     

Synthesis, Characterization and Properties of Novel Star-Shaped π-Conjugated Oligomers with Triphenylamine Core

Four new star‐shaped π‐conjugated oligomers ( TPA‐CZ3 , TPA‐TPA3 , TPA‐PTZ3 and TPA‐BT3 ) with triphenylamine as a core and different electron‐donating ability groups, carbazole, triphenylamine, phenothiazine and bithiophene, as peripheral units have been designed and synthesized via the Heck reaction. These oligomers show good solubility in common organic solvents. Their photophysical, electrochemical, electronic structure and charge transfer properties between these star‐shaped π‐conjugated oligomers and N,N′‐bis(1‐ethylpropyl)‐3,4:9,10‐perylene bis(tetracarboxyl diimide) (EP‐PDI) have been investigated by UV‐vis absorption spectra, photoluminescence (PL) spectra, cyclic voltammetry (CV) measurement, theoretical calculations and fluorescence quenching. The results show that the absorptions and fluorescences of TPA‐CZ3 , TPA‐TPA3 and TPA‐PTZ3 are red shifted with the electron‐donating ability of the peripheral unit increasing from carbazole to triphenylamine and phenothiazine. In addition, although the bithiophene group has a weaker electron‐donating ability than carbazole, triphenylamine and phenothiazine, the absorption and fluorescence of TPA‐BT3 have a red shift than those of TPA‐CZ3 , TPA‐TPA3 and TPA‐PTZ3 because TPA‐BT3 has a longer conjugation length than TPA‐CZ3 , TPA‐TPA3 and TPA‐PTZ3 . The triphenylamine core and the peripheral units can constitute a large conjugated structure. The fluorescence quenching properties indicate that efficient charge transfer can happen between the star‐shaped oligomers and EP‐PDI.     

环境科学与工程专业物理化学课程教与学的探讨

物理化学的学习前提是具有良好的高等数学知识基础及较强的逻辑推理能力,因此物理化学普遍被视为最难学的化学学科。本文紧扣金课标准,以环境科学与工程类专业学生为授课对象,基于近年来作者在物理化学教学内容和方法方面的探索,分析物理化学中的教与学中存在的问题及解决方法。     

CRISPR-Cas12a System for Biosensing and Gene Regulation

Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising technology in the biological world. As one of the CRISPR-associated (Cas) proteins, Cas12a is an RNA-guided nuclease in the type V CRISPR-Cas system, which has been a robust tool for gene editing. In addition, due to the discovery of target-binding-induced indiscriminate single-stranded DNase activity of Cas12a, CRISPR-Cas12a also exhibits great promise in biosensing. This minireview not only gives a brief introduction to the mechanism of CRISPR-Cas12a but also highlights the recent developments and applications in biosensing and gene regulation. Finally, future prospects of the CRISPR-Cas12a system are also discussed. We expect this minireview will inspire innovative work on the CRISPR-Cas12a system by making full use of its features and advantages.     

Modulating Protein–Protein Interactions by Cyclic and Macrocyclic Peptides. Prominent Strategies and Examples

Cyclic and macrocyclic peptides constitute advanced molecules for modulating protein–protein interactions (PPIs). Although still peptide derivatives, they are metabolically more stable than linear counterparts, and should have a lower degree of flexibility, with more defined secondary structure conformations that can be adapted to imitate protein interfaces. In this review, we analyze recent progress on the main methods to access cyclic/macrocyclic peptide derivatives, with emphasis in a few selected examples designed to interfere within PPIs. These types of peptides can be from natural origin, or prepared by biochemical or synthetic methodologies, and their design could be aided by computational approaches. Some advances to facilitate the permeability of these quite big molecules by conjugation with cell penetrating peptides, and the incorporation of β-amino acid and peptoid structures to improve metabolic stability, are also commented. It is predicted that this field of research could have an important future mission, running in parallel to the discovery of new, relevant PPIs involved in pathological processes.     

Variable fluid properties and variable heat flux effects on the flow and heat transfer in a non-Newtonian Maxwell fluid over an unsteady stretching sheet with slip velocity

The effects of variable fluid properties and variable heat flux on the flow and heat transfer of a non-Newtonian Maxwell fluid over an unsteady stretching sheet in the presence of slip velocity have been studied. The governing differential equations are transformed into a set of coupled non-linear ordinary differential equations and then solved with a numerical technique using appropriate boundary conditions for various physical parameters. The numerical solution for the governing non-linear boundary value problem is based on applying the fourth-order Runge-Kutta method coupled with the shooting technique over the entire range of physical parameters. The effects of various parameters like the viscosity parameter, thermal conductivity parameter, unsteadiness parameter, slip velocity parameter, the Deborah number, and the Prandtl number on the flow and temperature profiles as well as on the local skin-friction coefficient and the local Nusselt number are presented and discussed. Comparison of numerical results is made with the earlier published results under limiting cases.     

时间倾斜算子在离心压缩机动/静相干非定常模拟中的应用

本文介绍了用时间倾斜算子来处理非定常计算中非等栅距的方法。通过引入时间倾斜算子对N-S方程进行转化,而不对几何结构作任何改变,且所计算的叶片通道数小,以确保有较好的计算效率。粘性的影响被归类到源项中来进行求解,在作时间倾斜的方程转换时,就不用忽略粘性应力项的影响,使得方程的求解更为真实。同商用软件的计算结果进行了比较,结果表明应用本文所发展的程序,能很好的预测离心压缩机级的非定常流动。