RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ～40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ～90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).     

Structural and biochemical characterization of SADS‐CoV papain‐like protease 2

Swine acute diarrhea syndrome coronavirus (SADS‐CoV) is a novel coronavirus that is involved in severe diarrhea disease in piglets, causing considerable agricultural and economic loss in China. The emergence of this new coronavirus increases the importance of understanding SADS‐CoV as well as antivirals. Coronaviral proteases, including main proteases and papain‐like proteases (PLP), are attractive antiviral targets because of their essential roles in polyprotein processing and thus viral maturation. Here, we describe the biochemical and structural identification of recombinant SADS papain‐like protease 2 (PLP2) domain of nsp3. The SADS‐CoV PLP2 was shown to cleave nsp1 proteins and also peptides mimicking the nsp2|nsp3 cleavage site and also had deubiquitinating and deISGynating activity by in vitro assays. The crystal structure adopts an architecture resembling that of PLPs from other coronaviruses. We characterize both conserved and unique structural features likely directing the interaction of PLP2 with the substrates, including the tentative mapping of active site and other essential residues. These results provide a foundation for understanding the molecular basis of coronaviral PLPs' catalytic mechanism and for the screening and design of therapeutics to combat infection by SADS coronavirus.     

Flexible docking of peptides to proteins using CABS‐dock

Molecular docking of peptides to proteins can be a useful tool in the exploration of the possible peptide binding sites and poses. CABS‐dock is a method for protein–peptide docking that features significant conformational flexibility of both the peptide and the protein molecules during the peptide search for a binding site. The CABS‐dock has been made available as a web server and a standalone package. The web server is an easy to use tool with a simple web interface. The standalone package is a command‐line program dedicated to professional users. It offers a number of advanced features, analysis tools and support for large‐sized systems. In this article, we outline the current status of the CABS‐dock method, its recent developments, applications, and challenges ahead.     

Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2

Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐CoVs and Middle East Respiratory Syndrome coronavirus (MERS‐CoVs), the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high‐throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS‐CoV‐2 proteins and structures. Here we report two high‐resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.     

Developments,applications, and prospects of cryo‐electron microscopy

Cryo‐electron microscopy (cryo‐EM) is a structural biological method that is used to determine the 3D structures of biomacromolecules. After years of development, cryo‐EM has made great achievements, which has led to a revolution in structural biology. In this article, the principle, characteristics, history, current situation, workflow, and common problems of cryo‐EM are systematically reviewed. In addition, the new development direction of cryo‐EM—cryo‐electron tomography (cryo‐ET), is discussed in detail. Also, cryo‐EM is prospected from the following aspects: the structural analysis of small proteins, the improvement of resolution and efficiency, and the relationship between cryo‐EM and drug development. This review is dedicated to giving readers a comprehensive understanding of the development and application of cryo‐EM, and to bringing them new insights.     

不同色彩珙桐叶片和苞片解剖结构及色素含量比较研究

以生长于同一生境下的粉红珙桐(粉红色叶片、苞片)与普通珙桐(绿色叶片、白色苞片)为试材,对比两种色彩珙桐叶片/苞片解剖结构和色素含量的差异,以揭示珙桐色彩转变的规律。结果显示：(1)两种珙桐叶片均属于异面叶类型,栅栏组织由一层长柱形细胞整齐排列而成,海绵组织排列疏松,部分粉红叶片的上表皮细胞向外凸起,绿叶无此现象;粉红叶片的总厚度及其表皮角质层、栅栏组织和海绵组织厚度都高于绿叶,而表皮较薄。(2)两种珙桐苞片均无栅栏组织和海绵组织的分化,粉红苞片上表皮细胞明显隆起,上表皮角质层增厚,而下表皮变薄。(3)粉红叶片的类黄酮、花色苷含量分别是绿色叶片的1.52倍、3.67倍,两者的光合色素含量无显著差异,但粉红叶片的叶绿素a/b值比绿色叶低很多;粉红苞片花色苷含量显著高于白色苞片,而两者类黄酮含量差异不大。研究表明,花色苷是珙桐叶片和苞片色彩转红的直接因素,类黄酮有助于叶片呈红色;粉红珙桐叶片/苞片的解剖结构发生了一定变化,对光能的利用效率更高,对阴湿环境的适应性增强。     

结构稳定性: 概念、方法和应用

群落内物种间相互作用的结构是高度组织化的。群落结构对多物种共存的影响机制是群落生态学的核心科学问题之一。目前生态学界在这一问题上存在多种不同的观点。一个可能的原因是, 由于环境因子的复杂性, 大部分研究忽略了环境因子对群落结构和物种共存的重要影响。在这一背景下, 近期发展起来的结构稳定性理论系统地联系了群落结构、环境因子和物种共存, 并在此基础上建立了一个和经验数据紧密结合的理论框架。本文首先简要回顾了当前关于群落结构研究的争鸣, 然后介绍了结构稳定性的理论框架和计算方法, 最后详细介绍了结构稳定性理论在不同生态群落和不同生态学问题中的应用。在全球气候变化的背景下, 结构稳定性理论提供了一种新的视角来理解群落层面的生物多样性维持机制。     

杜鹃属植物与杜鹃灌丛群落的研究进展

对杜鹃属(Rhododendron L.)植物起源、中国分布、适应性、灌丛群落结构特征和演替特征等问题进行了综述,并对杜鹃属植物的深入研究和合理利用进行展望。中国西南地区以及喜马拉雅至缅甸北部地区为杜鹃属植物的起源中心,贵州百里杜鹃林是全球最大野生杜鹃资源库。杜鹃属植物的适应性与所在区系的同质性、海拔相似度、进化程度、关键功能性状等密切相关,基于进化-形态功能特征的比较为选育适应性优良的杜鹃品种提供了参考。杜鹃灌丛群落具有特殊性,表现出复杂的多层次垂直结构、镶嵌式水平结构和明显的年龄结构特征。依据群落具备优势种生态位宽度大且种群间的生态位相似性比例较小来判定杜鹃灌丛群落已演替至顶级的观点仍有待考证。     

兴隆山国家级自然保护区不同生境的蝴蝶群落结构与种-多度分布

为明确甘肃兴隆山国家级自然保护区内的蝴蝶种类, 以及不同生境的蝴蝶群落结构与种-多度分布的变化情况, 在全部5个林场选取6条样线, 于2015-2018年连续4年采用样线法对保护区的蝴蝶进行调查和采集, 并分析了其多样性指数及种-多度分布。4年共采集蝴蝶标本5,719号, 经鉴定隶属8科69属120种。眼蝶科(3,093号)是保护区的优势类群, 喙蝶科仅采集到1号标本(朴喙蝶, Libythea lepita), 为保护区的稀有种类。其中, 各样线的种数、个体数、多样性指数以及物种丰富度表现为: 样线I最高, 样线IV次之, 说明其生境结构稳定, 环境良好, 适合蝶类生存; 样线III蜜源植物丰富, 各项指数较高; 样线V海拔较高, 各项指数较低; 样线II植物群落结构单一, 各项指数最低。相似性系数分析结果表明: 样线I和VI、III和IV、III和VI均为中等相似; 其余各样线间为中等不相似。区系分析结果表明: 古北种有63种, 占总种数的52.5%; 东洋种2种, 占总种数的1.7%; 广布种55种, 占总种数的45.8%。说明古北种占绝对优势, 且明显高于东洋种, 具有很强的地区代表性。种-多度分布分析结果表明: 样线I和IV呈现出对数正态分布, 模型拟合效果较好; 样线II和VI为非典型的对数级数模型, 符合生态位优先占领假说。说明不同生境以及人为干扰因素与蝶类多样性关系密切, 表现出单一生态系统蝴蝶群落的多样性指数较低, 复杂生态系统其多样性指数较高的特点。