Virtual screening of eighteen million compounds against dengue virus: Combined molecular docking and molecular dynamics simulations study

Dengue virus is a major issue of tropical and sub-tropical regions. Dengue virus has been the cause behind the major alarming epidemics in the history with mass causalities from the decades. Unavailability of on-shelf drugs for the prevention of further proliferation of virus inside the human body results in immense number of deaths each year. This issue necessitates the design of novel anti-dengue drug. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of dengue virus. Therefore, approximately eighteen million compounds from the ZINC database have been virtually screened against nonstructural protein 3 (NS3). The incremental construction algorithm of Glide docking program has been used with its features high throughput virtual screening (HTVS), standard precision (SP), extra precision (XP) and in combination of Prime module, induced fit docking (IFD) approach has also been applied. Five top-ranked compounds were then selected from the IFD results with better predicted binding energies with the catalytic triad residues (His51, Asp75, and Ser135) that may act as potential inhibitors for the underlying target protease enzyme. The top-ranked compounds ZINC95518765, ZINC44921800, ZINC71917414, ZINC39500661, ZINC36681949 have shown the predicted binding energies of −7.55, −7.36, −8.04, −8.41, −9.18 kcal/mol, respectively, forming binding interactions with three catalytically important amino acids. Top-docking poses of compounds are then used in molecular dynamics (MD) simulations. In computational studies, our proposed compounds confirm promising results against all the four serotypes of dengue virus, strengthening the opportunity of these compounds to work as potential on-shelf drugs against dengue virus. Further experimentation on the proposed compounds can result in development of strong inhibitors.     

A dimension map for molecular aggregates

A pair of gyradius ratios, defined from the principal radii of gyration, are used to generate a dimension map that describes the geometry of molecular aggregates in water and in organic solvents. Molecular dynamics simulations were performed on the aggregation of representative biomolecules and polyaromatic compounds to demonstrate application of the dimension map. It was shown that molecular aggregate data on the dimension map were bounded by two boundary curves, and that the map could be separated into three regions representing three groups of structures: one-dimensional rod-like structures; two-dimensional planar structures or short-cylinder-like structures; and three-dimensional sphere-like structures. Examining the location of the aggregates on the dimension map and how the location changes with solvent type and solute material parameter provides a simple yet effective way to infer the aggregation manner and to study solubility and mechanism of aggregation.     

Beam search algorithms for the single machine total weighted tardiness scheduling problem with sequence-dependent setups

In this paper, we consider the single machine weighted tardiness scheduling problem with sequence-dependent setups. We present heuristic algorithms based on the beam search technique. These algorithms include classic beam search procedures, as well as the filtered and recovering variants. Previous beam search implementations use fixed beam and filter widths. We consider the usual fixed width algorithms, and develop new versions that use variable beam and filter widths.     

高压变频器在重钢步进梁式加热炉风机控制中的应用

本文介绍HARSVERT—A系列高压变频器在重钢宽厚板工程步进梁式加热炉风机功率控制中的应用,主要论述了所采用的高压变频器的原理及控制系统技术方案。     

一种改进的波束域ESPRIT算法

高分辨方位估计技术在声纳、雷达、通信、地质探测等众多应用领域中占有十分重要的地位.ESPRIT算法作为一种成熟的高分辨算法有运算量小的优点,但其减小了阵列的有效孔径,在现有的高分辨处理设备中,由于空间的限制,阵列不可能随意增大,因此要最大限度的扩大阵列的有效孔径.通过对均匀线列阵下波束域ESPRIT算法(BmESPRIT)的研究,提出了一种基于ESPRIT的新算法,并给出了转换成波束域处理的构造方法.该算法利用后向平移技术,使两子阵列与原阵列具有相同的有效孔径.有效的利用了阵列资源.仿真结果表明在相同条件下该算法的估计性能明显提高.     

Microstructure of sputtered epitaxial Ni0.80Fe0.20/NixCO1−xO exchange coupled bilayers on α-Al2O3 (0001)

Epitaxial Ni_0.80Fe_0.20/Ni_xCo_1−xO bilayers have been grown on α-Al₂O₃ (0001) substrates by dc-sputtering X-ray diffraction and transmission electron microscopy have been employed to characterize these exchange-coupled films. The x-ray diffraction spectrum shows only the (111) family of peaks in both Ni_0.80Fe_0.20 and Ni_xCO_1−xO films. Growth orientation relationships have been determined from diffraction patterns taken in planar view and cross section. The relationships are: (111) Ni_0.80Fe_0.20//(111) Ni_xCo_1−xO//(0001) α−Al₂O₃ and [1 0]Ni_0.80FE_0.20//[1 0]Ni_xCo_1-xO//[1 00] α-Al₂O₃. The microstructure of these films as well as the interfacial structure between Ni_0.80Fe_0.20 and Ni_xCo_1−xO have been analyzed in high resolution electron microscopy and are described in this paper. In addition, the dependence of the exchange coupling field on interfacial roughness is discussed.     

Low temperature annealing of metals with electrical wind force effects

Conventional annealing is a slow, high temperature process that involves heating atoms uniformly, i.e., in both defective and crystalline regions. This study explores an electrical alternative for energy efficiency,where moderate current density is used to generate electron wind force that produces the same outcome as the thermal annealing process. We demonstrate this on a zirconium alloy using in-situ electron back scattered diffraction(EBSD) inside a scanning electron microscope(SEM) and juxtaposing the results with that from thermal annealing. Contrary to common belief that resistive heating is the dominant factor, we show that 5 × 10~4 A/cm~2 current density can anneal the material in less than 15 min at only135?C. The resulting microstructure is essentially the same as that obtained with 600?C processing for360 min. We propose that unlike temperature, the electron wind force specifically targets the defective regions, which leads to unprecedented time and energy efficiency. This hypothesis was investigated with molecular dynamics simulation that implements mechanical equivalent of electron wind force to provide the atomistic insights on defect annihilation and grain growth.     

A characterization of (regular) circular languages generated by monotone complete splicing systems

Circular splicing systems are a formal model of a generative mechanism of circular words, inspired by a recombinant behaviour of circular DNA. Some unanswered questions are related to the computational power of such systems, and finding a characterization of the class of circular languages generated by circular splicing systems is still an open problem. In this paper we solve this problem for monotone complete systems, which are finite circular splicing systems with rules of a simpler form. We show that a circular language L is generated by a monotone complete system if and only if the set Lin(L) of all words corresponding to L is a pure unitary language generated by a set closed under the conjugacy relation. The class of pure unitary languages was introduced by A. Ehrenfeucht, D. Haussler, G. Rozenberg in 1983, as a subclass of the class of context-free languages, together with a characterization of regular pure unitary languages by means of a decidable property. As a direct consequence, we characterize (regular) circular languages generated by monotone complete systems. We can also decide whether the language generated by a monotone complete system is regular. Finally, we point out that monotone complete systems have the same computational power as finite simple systems, an easy type of circular splicing system defined in the literature from the very beginning, when only one rule of a specific type is allowed. From our results on monotone complete systems, it follows that finite simple systems generate a class of languages containing non-regular languages, showing the incorrectness of a longstanding result on simple systems.