Combining electronic properties and virtual screening for the development of new antioxidants: Trolox-like compounds as application example

Oxidative stress is an imbalance between the production of free radicals and the antioxidant defenses of the organism. Heart diseases, anemia, inflammation, and neurodegenerative disorders have been associated with this biological condition. Trolox is a notable antioxidant drug similar to vitamin E, and it is used to decrease the oxidative stress or repair the damage caused by it. In this work, the virtual screening technique is applied to identify compounds with antioxidant activities similar to Trolox. The antioxidant activity of these compounds was assessments by the mechanisms of hydrogen atom transfer and single electron transfer. Properties such as bond dissociation enthalpy, adiabatic ionization potential, Gibbs free reaction energy, spin density, highest occupied molecular orbital (HOMO), and GAP (HOMO-LUMO) energies, obtained from the DFT approach, point out to the predominance of the HAT mechanism for the antioxidant action of these compounds. The obtained results contribute to a better understanding of the chemical and physical properties responsible for antioxidant activity and the design of new antioxidant agents.     

Ensemble Docking Coupled to Linear Interaction Energy Calculations for Identification of Coronavirus Main Protease (3CLpro) Non-Covalent Small-Molecule Inhibitors

SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, represents a new strain of Coronaviridae. In the closing 2019 to early 2020 months, the virus caused a global pandemic of COVID-19 disease. We performed a virtual screening study in order to identify potential inhibitors of the SARS-CoV-2 main viral protease (3CL^pro or M^pro). For this purpose, we developed a novel approach using ensemble docking high-throughput virtual screening directly coupled with subsequent Linear Interaction Energy (LIE) calculations to maximize the conformational space sampling and to assess the binding affinity of identified inhibitors. A large database of small commercial compounds was prepared, and top-scoring hits were identified with two compounds singled out, namely 1-[(R)-2-(1,3-benzimidazol-2-yl)-1-pyrrolidinyl]-2-(4-methyl-1,4-diazepan-1-yl)-1-ethanone and [({(S)-1-[(1H-indol-2-yl)methyl]-3-pyrrolidinyl}methyl)amino](5-methyl-2H-pyrazol-3-yl)formaldehyde. Moreover, we obtained a favorable binding free energy of the identified compounds, and using contact analysis we confirmed their stable binding modes in the 3CL^pro active site. These compounds will facilitate further 3CL^pro inhibitor design.     

Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial. About 65% and 80% of microbial and chronic infections are associated with biofilm formation, respectively. The increase in infections by multi-resistant bacteria instigates the need for the discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD. For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the PleD protein and hence blocking the biofilm formation.     

Natural Products Extracted from Fungal Species as New Potential Anti-Cancer Drugs: A Structure-Based Drug Repurposing Approach Targeting HDAC7

Mushrooms can be considered a valuable source of natural bioactive compounds with potential polypharmacological effects due to their proven antimicrobial, antiviral, antitumor, and antioxidant activities. In order to identify new potential anticancer compounds, an in-house chemical database of molecules extracted from both edible and non-edible fungal species was employed in a virtual screening against the isoform 7 of the Histone deacetylase (HDAC). This target is known to be implicated in different cancer processes, and in particular in both breast and ovarian tumors. In this work, we proposed the ibotenic acid as lead compound for the development of novel HDAC7 inhibitors, due to its antiproliferative activity in human breast cancer cells (MCF-7). These promising results represent the starting point for the discovery and the optimization of new HDAC7 inhibitors and highlight the interesting opportunity to apply the “drug repositioning” paradigm also to natural compounds deriving from mushrooms.     

基于MIMO模型下的目标定位

Bekermani提出了一种新的空时编码方法,用于雷达或声纳等目标检测和定位系统,该方法将数字波束形成同时应用于天线阵元发射端和接收端。在此基础上,将该方法推广至多目标定位系统,利用该方法可以产生大量虚拟阵元,从而增加了可以检测到的目标数目,提高了阵元的利用率。通过计算机仿真,证明该方法的可行性。     

Drug Design—Past,Present, Future

Drug design is a complex pharmaceutical science with a long history. Many achievements have been made in the field of drug design since the end of 19th century, when Emil Fisher suggested that the drug–receptor interaction resembles the key and lock interplay. Gradually, drug design has been transformed into a coherent and well-organized science with a solid theoretical background and practical applications. Now, drug design is the most advanced approach for drug discovery. It utilizes the innovations in science and technology and includes them in its wide-ranging arsenal of methods and tools in order to achieve the main goal: discovery of effective, specific, non-toxic, safe and well-tolerated drugs. Drug design is one of the most intensively developing modern sciences and its progress is accelerated by the implication of artificial intelligence. The present review aims to capture some of the most important milestones in the development of drug design, to outline some of the most used current methods and to sketch the future perspective according to the author’s point of view. Without pretending to cover fully the wide range of drug design topics, the review introduces the reader to the content of Molecules’ Special Issue “Drug Design—Science and Practice”.     

移动式电子系统总体设计与电气布局

介绍了电子设备方舱基本总体设计流程及其相关的基本原则．论述了电气总体设计与电源选择、电磁兼容以及电缆布线设计、布线施工一致性的关系．提出了电子设备方舱总体设计的基本方法,并举例说明通过电缆布线设计解决电磁兼容问题的方法．     

半导体激光器电噪声的软件分析

对半导体激光器(LD)电噪声特性进行了小波分析,定位g-r噪声转折频率.根据LabVIEW6.0软件的虚拟仪器特性,设计了虚拟的FFT分析仪,实现LD电噪声的时域波形显示、谱分析、互谱分析、谱密度分析以及频率响应分析.     

基于虚拟仪器的视频图像采集系统设计

应用虚拟仪器技术,在Lab VIEW7．1开发平台上设计了利用IMAQ Vision for LabVIEW基于NI IMAQ 1405图像采集卡的图像采集系统。该系统对CCD电视、红外热像仪等输出的模拟视频图像具有采集能力,且结构简单,扩展方便,效率高,通用性强,显示了虚拟仪器技术的在信息技术研发中的显著优势。     

基于虚拟现实的光电对抗仿真系统的研究

将虚拟现实技术应用于光电对抗仿真领域,采用虚拟现实建模软件Multigen Creator进行视景建模,用视景管理软件OpenGVS来实现场景驱动,构建了一个载机光电对抗仿真系统,并介绍了用OpenGVS来开发光电对抗软件所需要解决的几个关键问题,包括目标的建模、视点的选取,碰撞的检测,以及爆炸效果的产生等。最后根据开发的仿真平台,对红外干扰弹的干扰策略进行了研究。