乙酰胆碱M3受体拮抗剂的从头设计

M3受体是人体内分布广泛的一种重要的毒蕈碱乙酰胆碱受体亚型,与膀胱过度活动症、心律失常、呼吸道及支气管疾病密切相关.设计与合成M3受体拮抗剂对于开发治疗相关疾病的药物具有重要理论意义和应用价值。本文采用同源模建方法,构建了人M3受体蛋白的三维结构,基于M3受体拮抗剂的结构构建了其药效团模型,其中较理想的模型含有6个药效团特征元素。利用药效团模型进行了虚拟筛选,虚拟筛选的数据库是本实验室构建的虚拟化合物库,发现了10个新型的对M3受体有拮抗作用的化合物。最后对这10个化合物进行了分子对接,根据对接结果,发现3个化合物对接能量及结合方式比较合理,为M3受体拮抗剂的合成研究及活性测定奠定了基础。     

彩色图像分割的FCM初始化方法

针对传统模糊C-均值聚类方法所存在的过度依赖初始聚类中心、计算复杂度高等问题,提出一种新的FCM初始化方法.首先,使用维纳滤波分别对图像的R、G、B分量进行预处理,待转换为LAB色彩空间后,通过二次分水岭方法获取图像的封闭区域,并计算各区域的质心;其次,利用自适应无监督的方法对质心进行筛选和合并,将合并结果作为FCM的初始聚类中心;最后,使用FCM方法进行分割.实验结果表明,该方法不仅能够获得较准确的聚类中心,减少了迭代次数和运算时间,而且能够更好地实现图像的准确分割.     

基于节点优先权和兴趣数据筛选的传感器网络分簇算法

无线传感器节点工作时仅由自身携带的电池供电,因此高效控制节点能耗可以延长整个网络生命周期,提高网络整体利用率。针对环境监测类场景,提出了一种基于节点优先权和兴趣数据筛选的分簇算法,该算法同时考虑了节点分布距离和剩余能量,将这两个属性换算成簇头选举的优先权权值。此外,在簇头确定后簇头通过相应的数据筛选方法对每一轮子节点发来的数据进行处理,有选择地将数据传到基站。仿真结果表明,该算法在能量控制方面有较好的表现,明显地延长了网络生命周期。     

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.     

基于筛选进化模型的指标体系建立方法

针对评估指标的优选和权重分配问题,借鉴生物进化思想,构建筛选进化模型SEM,在筛选中计算基于欧氏距离的数据可信度和基于评价信息熵的指标适应度,根据指标适应度选择优势指标进入指标初始集,对劣势指标执行交叉和变异操作形成新的备选指标集。经过多轮筛选后建立指标初始集,并依据指标适应度进行权重分配。实例分析表明了该方法的可行性和有效性。     

A multi-criteria trajectory-based parameter sampling strategy for the screening method of elementary effects

Environmental models are inherently complex and often characterized by high dimensionality. The method of elementary effects (EE) is one of the most widely used parameter screening technique implemented to reduce burden on computational resources required for thorough model evaluation. Due to issues like inefficient screening and excessive sampling time, the development of more effective EE sampling strategies has been a recent research focus. This paper presents a new sampling strategy - Sampling for Uniformity (SU) – based on the principles of meeting close-to-theoretical parameter distributions and maximizing trajectory spread. The performance of the SU relative to existing strategies was evaluated using a number of criteria including generated parameter distributions' uniformity, time efficiency, trajectory spread, and screening efficiency. The SU performed better than some trajectory-based benchmark strategies across the evaluation criteria, underlining the effectiveness of multi-criteria based sampling and the need to focus future efforts on exploring other combinations of sampling criteria.     

β-淀粉样多肽自聚集抑制剂的电化学筛选方法研究

β-淀粉样多肽（Amyloidbeta,Aβ）的聚集物具有神经细胞毒性,可导致神经元凋亡,从而诱导阿尔茨海默症（Alzheimer’s disease,AD）的发生。能够抑制AB自聚集行为的化合物称为AB自聚集抑制剂。该抑制剂可抑制Aβ有毒聚集物的产生,从而降低Aβ所引起的神经细胞毒性,对AD病有一定的治疗效果。因此。筛选AB自聚集抑制剂对于AD的治疗有着重要的意义。在数以千万计的化合物中,要筛选出对Aβ自聚集有抑制效果的化合物需要借助众多的仪器和研究方法。该文总结了筛选AB自聚集抑制剂的几种方法．重点综述了几种低成本、快速、灵敏的电化学筛选方法。Aβ自聚集抑制剂的筛选对临床上AD病的治疗提供了理论基础,为治疗AD病这一复杂科学问题的研究起到了促进作用。     

Structure based virtual screening-driven identification of monastrol as a potent urease inhibitor

Virtual screening uses computer based methods to discover new ligands on the basis of biological structures. Among all virtual screening methods structure based docking has received considerable attention. In an attempt to identify new ligands as urease inhibitors, structure-based virtual screening (SBVS) of an in-house database of 10,000 organic compounds was carried out. The X-ray crystallographic structure of Bacillus pasteurii (BP) in complex with acetohydroxamic acid (PDB Code 4UBP) was used as a protein structure. As a starting point, ~10,000 compounds of our in-house database were analyzed to check redundancy and the compounds found repeated were removed from the database. Finally 6993 compounds were docked into the active site of BP urease using GOLD and MOE-Dock software. A remarkable feature of this study was the identification of monastrol, a well-known KSP inhibitor already in clinical trials, as a novel urease inhibitor. The hits identified were further evaluated by molecular docking and on examination of the affinity predictions, twenty-seven analogs of monastrol were synthesized by a multicomponent Biginelli reaction followed by their in vitro screening as urease inhibitors. Finally twelve compounds were identified as new urease inhibitors. The excellent in vitro activity suggested that these compounds may serve as viable lead compounds for the treatment of urease related problems.     

基于改进样板机法的风光互补新能源电站容量配比优化

风光等新能源电站出力具有间歇性和波动性,合理的风光容量配比可以充分实现二者的互补。不准确的电站理论功率计算会影响风光真实特征的提取,进而导致较大的容量配比误差。本文在新能源电站理论功率计算所通常采用的样板机法基础上进行改进,首先对异常数据进行识别及重构,然后识别新能源电站中的异常样板机并更新样板机集合,进一步根据非样板机的实际运行情况选取动态信息窗,利用动态信息窗内样板机和非样板机的实测功率,对非样板机分组并动态识别每组非样板机的比例系数,从而计算新能源电站的理论功率。基于多年历史理论功率对新能源电站进行特征分析,模拟随机出力场景,并进行场景筛选,建立了基于源荷不匹配风险的风光配比优化方法。通过算例验证了改进样板机法的准确性,利用该方法得到西北某地区电网风、光伏电站多年的改进理论功率数据,并优化得到该地区的风光最优配比。