Individual recognition in mice mediated by major urinary proteins.

The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism.     

Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins.

The anticancer activity of cis-diamminedichloroplatinum(II) (cisplatin) arises from its ability to damage DNA, with the major adducts formed being intrastrand d(GpG) and d(ApG) crosslinks. These crosslinks bend and unwind the duplex, and the altered structure attracts high-mobility-group domain (HMG) and other proteins. This binding of HMG-domain proteins to cisplatin-modified DNA has been postulated to mediate the antitumour properties of the drug. Many HMG-domain proteins recognize altered DNA structures such as four-way junctions and cisplatin-modified DNA, but until now the molecular basis for this recognition was unknown. Here we describe mutagenesis, hydroxyl-radical footprinting and X-ray studies that elucidate the structure of a 1:1 cisplatin-modified DNA/HMG-domain complex. Domain A of the structure-specific HMG-domain protein HMG1 binds to the widened minor groove of a 16-base-pair DNA duplex containing a site-specific cis-[Pt(NH3)2[d(GpG)-N7(1),-N7(2)]] adduct. The DNA is strongly kinked at a hydrophobic notch created at the platinum-DNA crosslink and protein binding extends exclusively to the 3' side of the platinated strand. A phenylalanine residue at position 37 intercalates into a hydrophobic notch created at the platinum crosslinked d(GpG) site and binding of the domain is dramatically reduced in a mutant in which alanine is substituted for phenylalanine at this position.     

基于多尺度熵和支持向量机的局部放电模式识别

为了准确、可靠地有效识别电力变压器中绝缘劣化的严重程度和局部放电的位置,本文提出一种基于多尺度熵特征提取方法,采用支持向量机对放电类型进行模式识别。首先,利用多尺度熵对放电信号从定性和定量两个角度有效提取特征放电信号特征量;其次,将获得的特征信号输入支持向量机对放电类型进行模式识别。实验结果表明,该方法可以有效提取局部放电信号特征量。     

Microscopic origins of entropy, heat capacity and the glass transition in proteins

Internal motion is central to protein folding, to protein stability through the resulting residual entropy, and to protein function. Despite its importance, the precise nature of the internal motions of protein macromolecules remains a mystery. Here we report a survey of the temperature dependence of the fast dynamics of methyl-bearing side chains in a calmodulin-peptide complex using site-specific deuterium NMR relaxation methods. The amplitudes of motion had a markedly heterogeneous spectrum and segregated into three largely distinct classes. Other proteins studied at single temperatures tend to segregate similarly. Furthermore, a large variability in the degree of thermal activation of the dynamics in the calmodulin complex indicates a heterogeneous distribution of residual entropy and hence reveals the microscopic origins of heat capacity in proteins. These observations also point to an unexpected explanation for the low-temperature 'glass transition' of proteins. It is this transition that has been ascribed to the creation of protein motional modes that are responsible for biological activity.     

cis-trans recognition and subunit-specific degradation of short-lived proteins

The N-end rule, a code that relates the metabolic stability of a protein to the identity of its amino-terminal residue, is universal in that different versions of the N-end rule operate in mammals, yeast and bacteria (unpublished data). The N-end rule-based degradation signal comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We now show that, in a multisubunit protein, these two determinants can be located on different subunits and still target the protein for destruction. Moreover, in this case (trans recognition) only the subunit that bears the lysine determinant is actually degraded. Thus an oligomeric protein can contain both short-lived and long-lived subunits. These insights have functional and practical implications.     

Protein activity regulation by conformational entropy

How the interplay between protein structure and internal dynamics regulates protein function is poorly understood. Often, ligand binding, post-translational modifications and mutations modify protein activity in a manner that is not possible to rationalize solely on the basis of structural data. It is likely that changes in the internal motions of proteins have a major role in regulating protein activity, but the nature of their contributions remains elusive, especially in quantitative terms. Here we show that changes in conformational entropy can determine whether protein-ligand interactions will occur, even among protein complexes with identical binding interfaces. We have used NMR spectroscopy to determine the changes in structure and internal dynamics that are elicited by the binding of DNA to several variants of the catabolite activator protein (CAP) that differentially populate the inactive and active DNA-binding domain states. We found that the CAP variants have markedly different affinities for DNA, despite the CAP?DNA-binding interfaces being essentially identical in the various complexes. Combined with thermodynamic data, the results show that conformational entropy changes can inhibit the binding of CAP variants that are structurally poised for optimal DNA binding or can stimulate the binding activity of CAP variants that only transiently populate the DNA-binding-domain active state. Collectively, the data show how changes in fast internal dynamics (conformational entropy) and slow internal dynamics (energetically excited conformational states) can regulate binding activity in a way that cannot be predicted on the basis of the protein's ground-state structure.     

A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins

Ubiquitination is a post-translation modification in which ubiquitin chains or single ubiquitin molecules are appended to target proteins, giving rise to poly- or monoubiquitination, respectively. Polyubiquitination targets proteins for destruction by the proteasome. The role of monoubiquitination is less understood, although a function in membrane trafficking is emerging, at least in yeast. Here we report that a short amino-acid stretch at the carboxy-termini of the monoubiquitinated endocytic proteins Eps15 and eps15R is indispensable for their monoubiquitination. A similar sequence, also required for this modification, is found in other cytosolic endocytic proteins, such as epsins and Hrs. These sequences comprise a protein motif, UIM (ref. 6), which has been proposed to bind to ubiquitin. We confirm this for the UIMs of eps15, eps15R, epsins and Hrs. Thus, the same motif in several endocytic proteins is responsible for ubiquitin recognition and monoubiquitination. Our results predict the existence of a UIM:ubiquitin-based intracellular network. Eps15/eps15R, epsins and Hrs may function as adaptors between ubiquitinated membrane cargo and either the clathrin coat or other endocytic scaffolds. In addition, through their own ubiquitination, they may further contribute to the amplification of this network in the endocytic pathway.     

Molecularly imprinted polymer for theophylline retention and molecular recognition properties in capillary electrochromatography

0　IntroductionMolecularimprinting[1 ] isatechniquebasedoncreatingcavities,inahighlycross linkedpolymermatrix ,thatcorrespondtothesizeandshapeoftheprintmolecule .Themolecularrecognitioneffectisaconsequenceofthepresenceinthepolymerizationmixtureoftemplatemoleculescapableofestab lishingnon covalentinteractionswithmonomerandcross linkers.Molecularlyimprintedpolymers (MIPs)havebeenusedaschromatographicstationaryphases[2 ,3] includingcapillaryelec trochromatography ,asselectivematerialsforbiosenso…     

70种单质标准熵的研究

用lgM、(lgM)2等分子参数为独立参量,通过回归方法建立数学模型来预测70种单质的标准熵[Sm0/(J.mol-1.K-1)],其回归方程为:Sm0=-5.056 20.704lgM 4.019(lgM)2,R=1.000.其预测结果表明该模型的原理简单,方法实用,结果可靠.     

一种氨基酸分子识别主体的合成及其表征

合成了一种新的氨基酸分子手性识别主体N－2－（L－苯丙氨酸）－N，N’－1，3－（邻氨基苯胺）－1，3－二酮（简称L）合锌（Ⅱ）。经红外图谱、元素分析及旋光测定结果表明产物为预期的目标产物。通过紫外可见光谱分析表明该主体对D型、L型氨基酸分子有手性识别作用。     

人参皂甙引起的人红细胞膜蛋白沟象变化的圆二色谱研究

用圆二色技术研究了５种人参皂甙对人红细胞膜的作用。作为模型的人红细胞膜悬液含有相当于膜蛋白质量１／１３或更少的乙醇。加入５×１０－７～２．４×１０－４ｍｏｌ的人参皂甙Ｒｂ２、Ｒｃ、Ｒｄ、Ｒｅ、Ｒｇ１后，人红细胞膜圆二色［θ］２２２的幅值均有不同程度的增长，反映膜蛋白α－螺旋含量的增加。这意味着人参皂甙有使膜蛋白有序化的作用。人参的抗衰老作用可能与此有关。人参皂甙的水溶性是影响其膜有序化作用功效的一个重要因素，这种作用与温度没有依赖关系。     

罗丹明B分子印迹聚合物的分子识别与结合特性的研究

以罗丹明 B为印迹分子 ,丙烯酰胺为功能单体 ,乙二醇二甲基丙烯酸酯为交联剂 ,制备了对罗丹明 B有较好选择性的印迹聚合物 .利用静态平衡结合法和 Scatchard分析法研究了此印迹聚合物的结合能力和选择性 ,结果表明 ,以丙烯酰胺为功能单体的印迹聚合物中形成了两类不同的结合位点 ,计算了离解常数分别为 1 .87×1 0 - 5和 4.2 4× 1 0 - 4mol/L.对比罗丹明 S和罗丹明 6G的结合特性 ,该印迹聚合物呈现了较好的选择性     

拓扑优化中基于图论的邻接熵过滤方法

在拓扑优化中提出一种基于图论的邻接熵过滤方法,通过分析单元的邻接信息,对无效单元进行过滤,从而有效消除棋盘格现象并降低优化结构的网格依赖性.该方法具有数值实现简单、计算量小、适应复杂网格划分、兼容多种有限元求解器等优点.给出了采用邻接熵过滤法的拓扑优化程序流程,用Matlab程序和ANSYS参数化设计语言实现了算法,并通过典型算例证明了该方法的有效性.     

基于SVM的刻蚀工艺失效状态识别

针对反应离子刻蚀工艺,研究其状态监测与识别.采用主元分析(PCA)方法对原始数据进行降维,提取出有效的特征子集,再应用SVM建立失效状态的诊断识别模型,分析模型参数对失效状态的分类识别效果.采用主元分析法进行数据降维,从多监控量中提取影响最大的特征子集,再基于支持向量机(SVM)算法建立了失效状态的诊断识别模型,并分析了模型参数对失效状态的分类识别效果.研究结果验证了基于SVM方法的有效性,表明该模型具有高效的模式识别能力,可应用于存在小样本问题的其他半导体工艺状态分类和识别中.     

广义熵原理驱动下的股市演化

股市是一个远离均衡的复杂开放系统，组元之间有着复杂的相互作用，不同于机械保守系统中可还原的基本粒子，也不同于经典耗散系统中随机碰撞的布朗粒子．本文充分考虑股市系统中组元的复杂相互作用，定义系统的广义熵，指出控制股市运行的基本物理法则乃是广义熵最大原理，由此建立了股市演化的非线性动力学方程．论文最后结合具体案例对股市系统的演化进行了数值模拟，并对结果进行了深入的讨论和分析．     

手性联苯二甲酸分子裂缝对氨基酸衍生物的对映选择性识别

用差紫外光谱滴定法考察了新型分子裂缝1-3对D／L．氨基酸甲酯的手性识别性能,测定了主客体间的结合常数（k）和自由能变化（△G°）．结果表明,裂口分子主体对所考察的客体分子显示良好的手性识别作用,其对D-氨基酸甲酯的识别优于对L-氨基酸甲酯的识别,识别作用的主要推劫力为氢键,范德华力等的协同作用．讨论了主体与客体间形状、大小匹配和几何互补等因素,对形成超分子配合物的影响,并利用计算机分子模拟作为辅助手段对实验结果与现象进行了解释．     

鹅去氧胆酸分子裂缝对手性分子的识别性能研究

利用紫外可见光谱差光谱滴定法考察了新型鹅去氧胆酸分子裂缝1~4对D/L氨基酸甲酯的对映选择性识别性能.结果表明,分子裂缝1~4对所考察的氨基酸甲酯均具有识别能力,其对D-氨基酸甲酯的识别优于对L-氨基酸甲酯的识别.受体与底物间的大小、形状匹配,微环境效应等对识别性能均有重要影响.识别作用的主要推动力来自受体与底物之间的互补氢键,受体与底物芳环之间的π-π堆叠作用等非共价键作用力的协同作用.