Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study

Dengue is a major public health concern in tropical and subtropical countries of the world. There are no specific drugs available to treat dengue. Even though several candidates targeted both viral and host proteins to overcome dengue infection, they have not yet entered into the later stages of clinical trials. In order to design a drug for dengue fever, newly emerged fragment-based drug designing technique was applied. RNA-dependent RNA polymerase, which is essential for dengue viral replication is chosen as a drug target for dengue drug discovery. A cascade of methods, fragment screening, fragment growing, and fragment linking revealed the compound [2-(4-carbamoylpiperidin-1-yl)-2-oxoethyl]8-(1,3-benzothiazol-2-yl)naphthalene-1-carboxylate as a potent dengue viral polymerase inhibitor. Both strain energy and binding free energy calculations predicted that this could be a better inhibitor than the existing ones. Molecular dynamics simulation studies showed that the dengue polymerase–lead complex is stable and their interactions are consistent throughout the simulation. The hydrogen-bonded interactions formed by the residues Arg792, Thr794, Ser796, and Asn405 are the primary contributors for the stability and the rigidity of the polymerase–lead complex. This might keep the polymerase in closed conformation and thus inhibits viral replication. Hence, this might be a promising lead molecule for dengue drug designing. Further optimization of this lead molecule would result in a potent drug for dengue.     

丘陵区生态农业旅游的垂直景观生态研究

针对城郊丘陵区的地貌特征,生态农业旅游景观应按坡度和等高线布置,形成山顶水保林带、坡上桃树带、坡中枇杷带、坡下特种瓜果带、山底特色水域带的垂直生态景观模式。这种模式不仅具有良好的景观效果,也产生了很好的生态效益。试验区植被覆盖率显著提高,物种多样性得到了恢复,景观林带内的气温和土温降低、温度日变幅减少、空气相对湿度增加,这种效果由弱至强依次表现为农作地、水保林、经果林。果园自然生草、种植牧草后有利于降低土壤和空气温度、减少温度日变幅、增加空气相对湿度和防治水土流失的效果。     

高中生物探究式实验教学设计研究及案例分析

“探究式学习”促使学生的学习方式和教师的教学方式发生深刻的变革.阐述了探究式学习、实验操作技能和探究式实验教学模式这三个概念的内涵.同时,对高中生物一个重要的验证性实验“叶绿体中色素的提取和分离”进行了改进,实施了探究式实验教学设计并进行了教学实践以及分析,旨在探讨如何培养学生的实验操作技能.由此可得出结论:开展探究式实验教学,既能通过规范的实验操作,培养学生的实验操作技能,又能培养学生的综合探究能力并树立实事求是的科学态度;利用随堂式的实验教学评价,能很好发挥探究式学习的成效.     

KAISO inhibition: an atomic insight

In today’s world, the pursuit of a novel anti-cancer agent remains top priority because of the fact that the global burden of this malady is continuously increasing. Our work is no different from others in searching for new therapeutic solutions. To achieve this, we are looking into Epigenetics, the phenomenon governed by hypermethylation and hypomethylation of tumor suppressor genes and oncogenes, respectively. Our target for this study is an important intermediary methyl-CpG binding protein named kaiso. In our study, we have used the X-ray crystallographic structure of Kaiso for virtual screening and molecular dynamics simulations to study the binding modes of possible inhibitors. The C2H2 domain comprising LYS539 was used for screening the inter bio screen Database having 48,531 natural compounds. Our approach of using computer-aided drug designing methods helped us to remove the execrable compounds and narrowed our focus on a selected few for molecular simulation studies. The top ranked compound (chem. ID 28127) exhibited the highest binding affinity and was also found to be stable throughout the 20 ns timeframe. This compound is therefore a good starting point for developing strong inhibitors.     

基于生物多样性与生态系统服务功能的秦岭山系自然保护体系规划

生物多样性与生态系统服务是目前生态保护的两大主要目标,在保护区体系规划设计中兼顾两个保护目标有助于发挥自然保护区的综合效益。以生物多样性与生态系统服务功能都重要的秦岭山系为研究区域,在生物多样性、水源涵养和土壤保持重要性评估的基础上,通过空缺分析,提出了秦岭山系的保护区体系优化方案。研究结果表明,现有的自然保护区保护了33.5%的生物多样性极重要区,22.9%的水源涵养极重要区,但是只保护了7.4%的土壤保持极重要区;建议在秦岭主峰、秦岭西部和东南部分别建立自然保护区群和生态功能保护区,保护区面积占秦岭山系总面积的31.4%,使生物多样性、水源涵养、土壤保持的极重要区的保护比例达76.2%、70.5%和41.5%,生态保护效益得到提升。研究结果可以为秦岭山系生态保护政策的制定提供参考,同时对于其他地区自然保护体系规划、以及国家公园构建也具有重要的借鉴意义。     

建平县农业生态系统结构总体设计的研究

农业生态系统结构的总体设计是农业生产发展的客观要求,同时,也是保证农村经济不断增长和农村生态系统良性循环的一个非常重要问题。农业生态系统边界范围较大,具有多层次、多因素、多目标、多途径等复杂性,要想深刻剖析农业生态系统结构和功能的关系,必须用系统工程的观点和方法对农业生态系统的结构进行控制和管理。本文通过对建平县农业     

庭园生态经济系统设计及应用

庭园生态经济系统设计及应用刘东飙邓立平（湖南省益阳市农村能源办公室４１３０００）（湖南省南县农村能源办公室４１３２００）ＤｅｓｉｇｎｉｎｇＯｆＨｏｍｅＧａｒｄｅｎＥｃｏｌｏｍｉｃＳｙｓｔｅｍｗｉｔｈＭｅｔｈａｎｅＧｅｎｅｒａｔｉｎｇａｓａＴｉｅａｎｄ...     

Conformation of peptides constructed from achiral amino acid residues Aib and DeltaZPhe: computational study of the effect of L/D- Leu at terminal positions

Conformational studies of the peptides constructed from achiral amino acid residues Aib and Delta(Z)Phe (I) Ac-Aib-Delta(Z)Phe-NHMe (II), and Ac-(Aib-Delta(Z)Phe)(3)-NHMe; peptides III-VI having L-Leu or D-Leu at either the N- or the C-terminal position and of peptides VII-X having Leu residues in different enantiomeric combinations at both the N- and the C-terminal positions in peptide II have been studied to design the peptide with the required helical sense. Peptide II, as expected, adopts degenerate left- and right-handed helical structures. It has been shown that the peptides IV and VI having D-Leu at either the N or the C terminus can be realized in the right-handed helical structure with the phi,psi values of -20 degrees and -60 degrees for the Aib/Delta(Z)Phe residues. L-Leu and D- Leu at both the terminals in peptides VII and VIII, respectively, have hardly any effect as both the left- and the right-handed structures are found to be degenerate. Peptides III and IX can be realized in right- and left-handed helical structures, respectively, in solvents of low polarity whereas peptides V and X are predicted to be in the right-handed helical structures stabilized by carbonyl-carbonyl interactions without the formation of hydrogen bonds. The conformational states with the phi,psi values of 0 degrees and -85 degrees in peptide V are characterized by rise per residue of 2.03 A, rotation per residue of 117.5 degrees , and 3.06 residues per turn. In all peptides having Leu residue at the N terminus, the methyl moiety of the acetyl group is involved in the CH/pi interactions with the Cepsilon--Cdelta edge of the aromatic ring of Delta(Z)Phe (3) and the amino group NH of Delta(Z)Phe is involved in the NH/pi interactions with its own aromatic ring. The CH(3) groups of the Aib residues are also involved in CH/pi interactions with the i + 1th and i + 3th Delta(Z)Phe's aromatic side chains.     

改造的蜂毒素基因在毕赤酵母中分泌表达及培养条件研究

对蜂毒素基因进行改造后,通过PCR方法获得新蜂毒素基因(MEA),将其克隆到表达载体pPICZa—A,而后将重组表达载体pPICZa-A-MEA转化GS115,筛选获得重组酵母菌．对GS115-ME经甲醇诱导表达并对培养条件进行优化探讨．对改造的蜂毒素进行了溶血活性、热稳定性及酸碱稳定性测定．结果表明,蜂毒素基因成功地在毕赤酵母中表达,经改造的蜂毒素在保留了抗菌活性的同时溶血活性降低20倍左右,同时还具有良好的热稳定性和酸碱稳定性．