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bPE toolkit: toolkit for computational protein engineering. bPE工具箱:计算蛋白质工程的工具箱。
Pub Date : 2014-12-01 Epub Date: 2014-10-19 DOI: 10.1007/s11693-014-9156-4
Gaurav Jerath, Prakash Kishore Hazam, Vibin Ramakrishnan

We present a computational toolkit consisting of five utility tools, for performing basic operations on a protein structure file in PDB format. The toolkit consists of five different programs which can be integrated as part of a pipeline for computational protein structure characterization or as a standalone analysis package. The programs include tools for chirality check for amino acids (ProChiral), contact map generation (CoMa), data redundancy (DaRe), hydrogen bond potential energy (HyPE) and electrostatic interaction energy (EsInE). All programs in the toolkit can be accessed and downloaded through the following link: http://www.iitg.ac.in/bpetoolkit/.

我们提出了一个由五个实用工具组成的计算工具包,用于在PDB格式的蛋白质结构文件上执行基本操作。该工具包由五个不同的程序组成,可以作为计算蛋白质结构表征管道的一部分集成,也可以作为一个独立的分析包。这些程序包括氨基酸手性检查工具(ProChiral)、接触图生成工具(CoMa)、数据冗余工具(DaRe)、氢键势能工具(HyPE)和静电相互作用能工具(EsInE)。toolkit中的所有程序均可通过以下链接访问和下载:http://www.iitg.ac.in/bpetoolkit/。
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引用次数: 3
A computational study of dsDNA pairs and vibrational resonance in separating water. dsDNA对及其在分离水中振动共振的计算研究。
Pub Date : 2014-12-01 Epub Date: 2014-11-05 DOI: 10.1007/s11693-014-9157-3
Richard J Calloway, Michael D Proctor, Victor M Boyer, Samantha Napier

This article investigates the relationship between molecular sequence and dependent interacting behavior of molecular segment pairs and secondly, sequence dependent, vibrational resonance in surrounding normal saline, protein-free water. The development of a molecular model to explore these systems phenomena, the results of several nanoscale molecular dynamics simulations, and analysis of behavior of interacting ΦX174 double-stranded DNA segment pair models in various configurations are presented. Fourier analysis revealed intriguing vibration frequencies within the solvent plane between the segments, while subsequent frequency domain transformation of the time domain waveforms revealed statistically significant resonating harmonic signals in the THz range.

本文研究了分子序列与分子片段对依赖相互作用的关系,其次,研究了分子序列依赖的振动共振在生理盐水无蛋白水中的作用。本文介绍了一个分子模型的发展,以探索这些系统现象,几个纳米尺度分子动力学模拟的结果,以及相互作用的行为分析ΦX174双链DNA片段对模型在不同的配置。傅里叶分析揭示了在段之间的溶剂平面内有趣的振动频率,而随后的时域波形的频域变换揭示了在太赫兹范围内具有统计学意义的谐振谐波信号。
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引用次数: 0
Information processing in the adaptation of Saccharomyces cerevisiae to osmotic stress: an analysis of the phosphorelay system. 酿酒酵母菌适应渗透胁迫的信息处理:磷接力系统的分析。
Pub Date : 2014-12-01 Epub Date: 2014-04-19 DOI: 10.1007/s11693-014-9146-6
Friedemann Uschner, Edda Klipp

Cellular signaling is key for organisms to survive immediate stresses from fluctuating environments as well as relaying important information about external stimuli. Effective mechanisms have evolved to ensure appropriate responses for an optimal adaptation process. For them to be functional despite the noise that occurs in biochemical transmission, the cell needs to be able to infer reliably what was sensed in the first place. For example Saccharomyces cerevisiae are able to adjust their response to osmotic shock depending on the severity of the shock and initiate responses that lead to near perfect adaptation of the cell. We investigate the Sln1-Ypd1-Ssk1-phosphorelay as a module in the high-osmolarity glycerol pathway by incorporating a stochastic model. Within this framework, we can imitate the noisy perception of the cell and interpret the phosphorelay as an information transmitting channel in the sense of C.E. Shannon's "Information Theory". We refer to the channel capacity as a measure to quantify and investigate the transmission properties of this system, enabling us to draw conclusions on viable parameter sets for modeling the system.

细胞信号是生物体在波动环境中生存的关键,也是传递有关外部刺激的重要信息的关键。已经形成了有效的机制,以确保对最佳适应进程作出适当的反应。为了使它们在生化传递过程中不受干扰地发挥作用,细胞需要能够可靠地推断出最初感知到的是什么。例如,酿酒酵母菌能够根据冲击的严重程度调整其对渗透休克的反应,并启动导致细胞接近完美适应的反应。我们通过结合随机模型研究了sln1 - ypd1 - ssk1 -磷接力作为高渗透压甘油途径中的一个模块。在这个框架下,我们可以模仿细胞的噪声感知,将磷接力解释为C.E.香农“信息论”意义上的信息传递通道。我们将信道容量作为量化和研究该系统传输特性的一种度量,使我们能够得出用于系统建模的可行参数集的结论。
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引用次数: 9
Statistical approach for lysosomal membrane proteins (LMPs) identification. 溶酶体膜蛋白(LMPs)鉴定的统计方法。
Pub Date : 2014-12-01 Epub Date: 2014-08-02 DOI: 10.1007/s11693-014-9153-7
Vijay Tripathi, Pooja Tripathi, Dwijendra Gupta

Discrimination of Lysosomal membrane proteins (LMP's) from folding types of globular (GPs) and other membrane proteins (OtMPs) is an important task both for identifying LMPs from genomic sequences and for the successful prediction of their secondary and tertiary structures. We have systematically analyzed the amino acid frequencies as well as dipeptide count of GPs, LMPs and OtMPs. Based on the above calculated single amino acid frequency combined with dipeptide count information, we statistically discriminated LMPs from GPs and OtMPs. This approach correctly classified the LMPs with an accuracy of 95 %. On the other hand, the amino acid frequency alone can discriminate LMPs with an accuracy of only 79 %. Similarly dipeptide count alone has an accuracy of 87 % for the discrimination of LMPs. Thus the combined information of both amino acid frequencies and dipeptide composition gives us significant high accurate results.

将溶酶体膜蛋白(LMP)与折叠类型的球蛋白(GPs)和其他膜蛋白(OtMPs)区分开来,对于从基因组序列中识别 LMPs 以及成功预测其二级和三级结构都是一项重要任务。我们对 GPs、LMPs 和 OtMPs 的氨基酸频率和二肽数量进行了系统分析。根据上述计算出的单个氨基酸频率和二肽数量信息,我们对 LMPs 和 GPs 及 OtMPs 进行了统计判别。这种方法对 LMPs 的正确分类准确率高达 95%。另一方面,仅凭氨基酸频率来区分 LMP 的准确率仅为 79%。同样,仅用二肽数量来区分 LMP 的准确率为 87%。因此,氨基酸频率和二肽组成的综合信息可为我们提供显著的高精确度结果。
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引用次数: 0
Virus proteins similar to human proteins as possible disturbance on human pathways. 病毒蛋白质与人类蛋白质相似,可能干扰人类途径。
Pub Date : 2014-12-01 Epub Date: 2014-05-24 DOI: 10.1007/s11693-014-9141-y
Zhao Jin, Masaaki Kotera, Susumu Goto

Cancer is not rare anywhere in the world now, and the global burden of cancer continues to increase largely every year. Previous research on infections and cancers reported that, about 17.8 % of the cancers worldwide, which are over 1.9 million cases of cancer, are related to viral infections. At least six oncoviruses, cancer-causing viruses, have been known so far, which include hepatitis B virus, hepatitis C virus, Epstein-Barr virus (EBV or HHV-4), human papillomavirus, human T lymphotropic virus type 1, Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8), but the pathogenic mechanism is far from being completely understood. In this study, assuming that finding human proteins significantly similar to viral oncoproteins leads to a categorization of the cancer-related pathways that are currently not clearly known, we analyzed different types of virus-caused cancers based on their similarity in order to clarify the unknown cancer mechanisms. As a result, we obtained several potential tumor pathways that may be significant and essential in oncogenic cancer process, which will be helpful for further study on cancer mechanisms and the development of new drug targets.

现在,癌症在世界上任何地方都不罕见,全球癌症负担每年都在大幅增加。先前关于感染和癌症的研究报告称,全球约17.8%的癌症,即190多万例癌症病例,与病毒感染有关。迄今为止,已知的致癌病毒至少有6种,包括乙型肝炎病毒、丙型肝炎病毒、eb病毒(EBV或HHV-4)、人乳头瘤病毒、人T淋巴细胞1型病毒、卡波西肉瘤相关疱疹病毒(KSHV或HHV-8),但其致病机制尚不完全清楚。在本研究中,假设发现与病毒癌蛋白显著相似的人类蛋白会导致目前尚不清楚的癌症相关途径的分类,我们根据它们的相似性分析了不同类型的病毒引起的癌症,以阐明未知的癌症机制。因此,我们获得了几个潜在的肿瘤通路,这些通路可能在癌变过程中具有重要和必要的意义,这将有助于进一步研究癌变机制和开发新的药物靶点。
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引用次数: 3
Recent advances and opportunities in synthetic logic gates engineering in living cells. 活细胞合成逻辑门工程的最新进展与机遇。
Pub Date : 2014-12-01 Epub Date: 2014-08-28 DOI: 10.1007/s11693-014-9154-6
Vijai Singh

Recently, a number of synthetic biologic gates including AND, OR, NOR, NOT, XOR and NAND have been engineered and characterized in a wide range of hosts. The hope in the emerging synthetic biology community is to construct an inventory of well-characterized parts and install distinct gene and circuit behaviours that are externally controllable. Though the field is still growing and major successes are yet to emerge, the payoffs are predicted to be significant. In this review, we highlight specific examples of logic gates engineering with applications towards fundamental understanding of network complexity and generating a novel socially useful applications.

近年来,包括AND, OR, NOR, NOT, XOR和NAND在内的许多合成生物门已经在广泛的宿主中被设计和表征。新兴合成生物学社区的希望是构建一个具有良好特征的部件清单,并安装外部可控的独特基因和电路行为。尽管该领域仍在发展,尚未取得重大成功,但预计其回报将是巨大的。在这篇综述中,我们重点介绍了逻辑门工程的具体例子,这些例子具有对网络复杂性的基本理解和产生新的社会有用应用的应用。
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引用次数: 57
Cartoons on bacterial balloons: scientists' opinion on the popularization of synthetic biology. 细菌气球上的漫画:科学家对普及合成生物学的看法。
Pub Date : 2014-12-01 Epub Date: 2014-10-08 DOI: 10.1007/s11693-014-9155-5
Martí Domínguez, Anna Mateu, Helge Torgersen, Manuel Porcar

How do scientists perceive the media coverage of synthetic biology (SB)? In this paper, we approach this question by studying a set of cartoons devoted to SB. Based on a categorization of the cartoons into five large thematic groups an international survey was carried out to assess the opinion of SB research groups on science communication with regard to the public image of their discipline. The 101 responses obtained indicate that in general, their perception of the communication is not negative, although many respondents raised concerns on the media's inclination to sensationalism and over-simplification. However, the results also suggest that (in the light of the unfortunate experiences with GMO communication) scientists should think twice before proposing metaphorical interpretations of their research.

科学家如何看待媒体对合成生物学(SB)的报道?在本文中,我们通过研究一组有关合成生物学的漫画来探讨这一问题。在将漫画分为五大主题组的基础上,我们开展了一项国际调查,以评估合成生物学研究小组对科学传播对其学科公众形象的影响的看法。101 份答复表明,总体而言,他们对传播的看法并不消极,尽管许多答复者对媒体的煽 情倾向和过度简单化表示担忧。不过,结果也表明,(鉴于转基因生物传播的不幸经历)科学家在对其研究提出隐喻性解释之前应三思而后行。
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引用次数: 0
Mechanisms of cell division as regulators of acute immune response. 细胞分裂作为急性免疫反应调节器的机制。
Pub Date : 2014-09-01 Epub Date: 2014-04-29 DOI: 10.1007/s11693-014-9149-3
Andrey Kan, Philip D Hodgkin

The acute adaptive immune response is complex, proceeding through phases of activation of quiescent lymphocytes, rapid expansion by cell division and cell differentiation, cessation of division and eventual death of greater than 95 % of the newly generated population. Control of the response is not central but appears to operate as a distributed process where global patterns reliably emerge as a result of collective behaviour of a large number of autonomous cells. In this review, we highlight evidence that competing intracellular timed processes underlie the distribution of individual fates and control cell proliferation, cessation and loss. These principles can be captured in a mathematical model to illustrate consistency with previously published experimentally observed data.

急性适应性免疫反应非常复杂,要经历静止淋巴细胞激活、细胞分裂和细胞分化快速扩张、分裂停止以及最终超过 95% 的新生成细胞死亡等阶段。这种反应的控制不是集中式的,似乎是一个分布式的过程,在这个过程中,大量自主细胞的集体行为导致可靠的全球模式出现。在这篇综述中,我们将重点介绍细胞内相互竞争的定时过程是个体命运分布和控制细胞增殖、停止和消失的基础。这些原理可以用数学模型来捕捉,以说明与之前发表的实验观察数据的一致性。
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引用次数: 0
Swinging a sword: how microtubules search for their targets. 挥剑:微管如何寻找它们的目标。
Pub Date : 2014-09-01 Epub Date: 2014-02-16 DOI: 10.1007/s11693-014-9134-x
Nenad Pavin, Iva M Tolić-Nørrelykke

The cell interior is in constant movement, which is to a large extent determined by microtubules, thin and long filaments that permeate the cytoplasm. To move large objects, microtubules need to connect them to the site of their destination. For example, during cell division, microtubules connect chromosomes with the spindle poles via kinetochores, protein complexes on the chromosomes. A general question is how microtubules, while being bound to one structure, find the target that needs to be connected to this structure. Here we review the mechanisms of how microtubules search for kinetochores, with emphasis on the recently discovered microtubule feature to explore space by pivoting around the spindle pole. In addition to accelerating the search for kinetochores, pivoting helps the microtubules to search for cortical anchors, as well as to self-organize into parallel arrays and asters to target specific regions of the cell. Thus, microtubule pivoting constitutes a mechanism by which they locate targets in different cellular contexts.

细胞内部是不断运动的,这在很大程度上是由渗透在细胞质中的微管、细长丝所决定的。为了移动大型物体,微管需要将它们连接到目的地。例如,在细胞分裂过程中,微管通过着丝点(染色体上的蛋白质复合体)将染色体与纺锤体极点连接起来。一个普遍的问题是,当微管被绑定到一个结构时,如何找到需要连接到这个结构的目标。在这里,我们回顾了微管如何搜索着丝点的机制,重点介绍了最近发现的微管特征,即通过绕主轴杆旋转来探索空间。除了加速寻找着丝点外,旋转还有助于微管寻找皮质锚点,以及自组织成平行阵列和瞄准细胞的特定区域。因此,微管旋转构成了一种在不同细胞环境中定位靶标的机制。
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引用次数: 24
Experiments inside a box lead to out-of-the-box ideas on cellular organization. 盒子里的实验带来了关于细胞组织的不同寻常的想法。
Pub Date : 2014-09-01 Epub Date: 2014-03-26 DOI: 10.1007/s11693-014-9139-5
Liedewij Laan

Microtubules are biopolymers that assemble from tubulin dimers into hollow tubes and play an important role in cellular organization. Their fascinating properties and variety of functions, like for example chromosome segregation, sperm propagation and polarity establishment, have made them a popular subject of study. In this perspective I focus on the contribution of minimal in vitro systems to our understanding of microtubule organization within the physical confinement of a cell.

微管是由微管蛋白二聚体组装成中空管的生物聚合物,在细胞组织中起着重要作用。它们迷人的特性和各种各样的功能,如染色体分离、精子繁殖和极性建立,使它们成为一个热门的研究课题。从这个角度来看,我专注于最小的体外系统对我们理解细胞物理限制内的微管组织的贡献。
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引用次数: 0
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Systems and Synthetic Biology
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