Similar,or dissimilar,that is the question. How different are methods for comparison of compounds similarity?

Comparison of compounds similarity is one of the main strategies of virtual screening protocols. Both similarity and dissimilarity concepts are of great importance during the search for new active compounds. Similarity is important due to the assumption that underlies the process of searching for new drug candidates: structurally similar compounds should induce similar biological response. On the other hand, we are also interested in dissimilarity, as we usually aim to find structurally novel ligands. In the study, we compared several approaches of evaluating compound similarity. Various representations and metrics were applied and we indicated the rate of variation of the results that can occur when shifting from one strategy to another. We compared both general similarity of datasets using different approaches, as well as examined the changes in the set of nearest neighbors when changing one compound representation into another, and the influence of representation/metric settings on the clustering outcome. We hope that the study will be of great help during the preparation of virtual screening experiments, stressing the need for careful selection of the way, the compound similarity is assessed. The differences in the results that can be obtained via the application of particular strategy can significantly influence the outcome of comparison studies; therefore, its settings should be carefully selected beforerunning the comparison.     

A transflective polymer-stabilised blue-phase liquid display with partitioned wall-shaped electrodes

A transflective polymer-stabilised blue-phase liquid crystal display (BP-LCD) with partitioned wall-shaped electrodes is proposed. The etched polymer layer contributes to balance the optical phase retardation between transmissive (T) and reflective (R) regions. The partitioned wall-shaped electrodes generate uniform and horizontal fields throughout the entire LC layer to induce isotropic-to-anisotropic transition in the blue-phase liquid crystal medium through Kerr effect. Consequently, the accumulated phase retardation along beam path is large, resulting in reasonable low operation voltage and high transmittance both in T and R regions. This approach enables the BP-LCD to be addressed by amorphous silicon thin-film transistors. Moreover, it exhibits wide viewing angle and a well-matched gamma curve.     

Blue-phase liquid crystal display with insulating protrusion

In order to lower the saturation voltage and enhance the transmittance of in-plane switching blue-phase liquid crystal display (IPS-BPLCD), IPS-BPLCD with insulating protrusion is proposed. The single-protrusion (only set on the top of pixel electrode) and double-protrusion (set on the top of pixel and common electrodes) structures are investigated in this work. The potential distribution changes when the protrusion is used. There is a thicker transverse electric field in BPLC range, because the stronger electric field at the edges of the electrodes is decentralised into BPLC range. As a result, the saturation voltage is reduced from 36.3 V to 28.9 V when the double-protrusion structure is used, and transmittance is increased by ~20%. The contrast ratio is larger than 1000:1 in 60° viewing cone using a half-wave biaxial film. Both single-protrusion and double-protrusion structures have the uniform gamma curves at large oblique viewing angles. Moreover, the off-axis image distortion index is 0.1590 at 60º polar angle when zigzag electrodes are used.     

Selection of phage-displayed antibodies with high affinity and specificity by electrophoresis in microfluidic devices

A method development aimed for high-throughput and automated antibody screening holds great potential for areas ranging from fundamental molecular interactions to the discovery of novel disease markers, therapeutic targets, and monoclonal antibody engineering. Surface display techniques enable efficient manipulation of large molecular libraries in small volumes. Specifically, phage display appeared as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities. Here, we present a phage-selection microfluidic device wherein electrophoresis was performed under two orthogonal electric fields through an agarose gel functionalized with the respective antigen. This microdevice was capable of screening and sorting in a single round high-affinity phage-displayed antibodies against virus glycoproteins, including human immunodeficiency virus-1 glycoprotein 120 or the Ebola virus glycoprotein (EBOV-GP). Phages were differentially and laterally swept depending on their antigen affinity; the high-affinity phages were recovered at channels proximal to the application site, whereas low-affinity phages migrated distal after electrophoresis. These experiments proved that the microfluidic device specifically designed for phage-selection is rapid, sensitive, and effective. Therefore, this is an efficient and cost-effective method that allowed highly controlled assay conditions for isolating and sorting high-affinity ligands displayed in phages.     

基于结构虚拟筛选发现蛋白质精氨酸甲基转移酶5抑制剂

蛋白质精氨酸甲基转移酶5(PRMT5)是蛋白质甲基转移酶家族(PRMTs)的重要一员,其主要生理功能是催化精氨酸单对称二甲基化。PRMT5的上调发生在不同类型的肿瘤中,并与不良预后密切相关,已被视为肿瘤治疗中的潜在靶点。近年来,已有多种PRMT5抑制剂进入临床试验,但目前尚未有药物获批上市。本研究基于Glide对接的虚拟筛选和生物活性实验,发现化合物8018-1271对PRMT5酶的抑制活性IC₅₀值为13.56±0.86μmol/L,并通过分子动力学揭示其与PRMT5蛋白结构域的相互作用模式。本研究所得化合物8018-1271可作为进一步改造的先导化合物,为新型PRMT5抑制剂的发现提供参考。     

Study of polymer-stabilised blue phase liquid crystal on a single substrate

One outstanding feature of the polymer-stabilised blue phase (PSBP) is that it is unnecessary to form an alignment film, which requires a high-temperature baking process. Therefore, PSBPs may enable flexible liquid crystal displays (LCDs) on plastic substrates. In this study, polymer stabilisation of a blue phase (BP) on a single substrate was performed without using a conventional sandwich-type cell, and the electro-optical properties are demonstrated to be similar to those of a sandwich-type PSBP LCD cell. It was experimentally shown that the oxygen which inhibits radical polymerisation is required to be excluded in order to complete the polymer stabilisation in blue phase.     

基于WebGL的舰船模拟训练虚拟三维技术应用

由于目前国内的舰船模拟训练系统大多均为岸基模拟器,和半实物半仿真的应用模式,受制于该传统方式下系统通用性、可扩展性差,成本高等局限性;提出一种基于WebGL的舰船模拟训练虚拟三维环境,采用其应用框架Three.js图形引擎库在网页中绘制3D虚拟交互界面,可直接通过浏览器登录系统,从而给出了可跨平台免插件高效的舰船模拟训练界面;结果表明该方法在人机交互界面的友好性、监控的直观性、训练操作的便捷性、较强的沉浸性等方面具有优势,亦可推广应用于其他模拟训练领域。     

基于Unity 3D的船舶压缩空气系统的虚拟设计

针对目前船舶空气压缩仿真训练系统大多采用半物理仿真与二维软件界面仿真相结合方式训练效果不佳的问题,将虚拟现实技术引入到船舶压缩空气系统的仿真设计;设计一套基于Unity 3D的船舶压缩空气系统,实现虚拟仿真程序和三维虚拟场景的实时交互,生成一个逼真的三维视觉、听觉、触觉的感官世界,加强培训人员的沉浸感,从而获得一种置身于真实环境中的感受;系统可供学员无限制反复训练,节省系统的维护费用,规避实物操作设备中可能出现的各种风险,提高训练效果。