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国家自然科学基金(11021463)

作品数:5 被引量:4H指数:1
相关作者:周璐金凤夏斌来鲁华魏平更多>>
相关机构:北京大学复旦大学更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划国家高技术研究发展计划更多>>
相关领域:生物学医药卫生更多>>

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Mean field study of a propagation-turnover lattice model for the dynamics of histone marking
2017年
We present a mean field study of a propagation-tumover lattice model, which was proposed by Hodges and Crabtree [Proc. Nat. Acad. Sci. 109, 13296 (2012)] for understanding how posttranslational histone marks modulate gene expression in mammalian ceils. The kinetics of the lattice model consists of nucleation, propagation and turnover mechanisms, and exhibits second-order phase transition for the histone marking domain. We showed rigorously that the dynamics essentially depends on a non-dimensional parameter k = k+/k-, the ratio between the propagation and turnover rates, which has been observed in the simulations. We then studied the lowest order mean field approximation, and observed the phase transition with an analytically obtained critical parameter. The boundary layer analysis was utilized to investigate the structure of the decay profile of the mark density. We also studied the higher order mean field approximation to achieve sharper estimate of the critical transition parameter and more detailed features. The comparison between the simulation and theoretical results shows the validity of our theory.
Fan YaoFangTing LiTieJun Li
M^(pro)-C蛋白三维结构域交换的机理:来自分子模拟的线索(英文)被引量:1
2012年
SARS冠状病毒主蛋白酶(Mpro)在病毒的蛋白酶切过程中发挥着重要作用.Mpro的晶体结构显示它存在两种形式的二聚体:一种是发生三维结构域交换的形式,另一种是非交换的形式.Mpro的C端结构域(Mpro-C)单独表达时也能形成与全长Mpro类似的三维结构域交换二聚体.三维结构域交换通常发生在蛋白质的表面,但Mpro-C的结构域交换却发生在疏水核心.在本文中,我们利用分子动力学模拟及三维结构域交换预测算法研究了Mpro-C中被高度埋藏的核心螺旋片段发生交换的机理.我们发现基于结构与基于序列的已有算法都不能正确预言出Mpro-C和Mpro中发生结构域交换的铰链区位置.分子模拟结果表明Mpro-C中的交换片段在天然态下埋藏得很好,但在变性单体中则会被释放并暴露在外面.因此,在完全或部分解折叠状态下交换片段的打开有助于促进单体间的相互作用及结构域交换二聚体的形成.
黄永棋康雪夏斌刘志荣
关键词:SARS冠状病毒分子模拟蛋白质-蛋白质相互作用
Functional genomic analysis of Hawaii marine metagenomes被引量:1
2015年
Using high-throughput sequencing on metagenome to analyze marine microbial community, it is one of current main issues in the field of environmental microbe research. In this paper, we conducted the functional analysis on seven samples of metagenomic data from different depth seawater in Hawaii. The results of gene prediction and function annotation indicate that there are large amounts of potential novel genes of which functions remain unknown at present. Based on the gene annotation, codon usage bias is studied on ribosomal protein-related genes and shows an evident influence by the marine extreme environment. Furthermore, focusing on the marine environmental differences such as light intensity, dissolved oxygen, temperature and pressure among various depths, comparative analysis is carried out on related genes and metabolic pathways. Thus, the understanding as well as new insights into the correlation between marine environment and microbes are proposed at molecular level. Therefore, the studies herein afford a clue to reveal the special living strategies of microbial community from sea surface to deep sea.
王晓琦王琦郭潇刘璐瀛郭江涛姚锦仙朱怀球
靛红类双功能抑制剂:调控SARS-3CL蛋白酶聚集状态与活性(英文)被引量:1
2012年
1-(2-萘甲基)靛红-5-甲酰胺类化合物通过与底物口袋结合来抑制SARS-3CL蛋白酶的活性,而SARS-3CL蛋白酶自身的N端8肽是作用于蛋白二聚界面的抑制剂.本文设计同时占据SARS-3CL蛋白酶底物口袋和二聚界面的双功能抑制剂,通过固相多肽合成方法制备由1-(2-萘甲基)靛红-5-甲酸和N端8肽组成的化合物,得到不同长度连接链的6个目标产物.用显色底物方法测定化合物对SARS-3CL蛋白酶的抑制活性,其中化合物3的活性最高,IC50值(半抑制率)为3.8μmol·L-1,连接偶数甘氨酸的活性明显要好于连接奇数甘氨酸的化合物.用超速离心沉降速率方法研究了化合物3对SARS-3CL蛋白酶聚集状态与活性的调控作用,其同时具有诱导与抑制二聚的双重能力,综合调控结果是抑制SARS-3CL蛋白酶的二聚.这项研究给应用合成的化合物研究酶活性调节机制提供了一个示例.
周璐金凤刘莹尚尔昌魏平李春梅来鲁华
Computational design of proteins with novel structure and functions被引量:1
2016年
Computational design of proteins is a relatively new field, where scientists search the enormous sequence space for sequences that can fold into desired structure and perform desired functions. With the computational approach, proteins can be designed, for example, as regulators of biological processes, novel enzymes, or as biotherapeutics. These approaches not only provide valuable information for understanding of sequence-structure-function relations in proteins, but also hold promise for applications to protein engineering and biomedical research. In this review, we briefly introduce the rationale for computational protein design, then summarize the recent progress in this field, including de novo protein design, enzyme design, and design of protein-protein interactions. Challenges and future prospects of this field are also discussed.
杨为来鲁华
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