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1.
基于DNA序列的3D图形表示,通过L/L矩阵的规范化最大特征值组成的3维向量来刻画了DNA序列,并基于这种方法,用β-globin基因的第一个外显子分析了11个物种的相似性问题。  相似文献   

2.
为了更多地挖掘隐藏在蛋白质序列中的信息,本研究将20种氨基酸均匀地排列在单位圆周上,得到每种氨基酸对应的二维坐标,再与氨基酸的6个理化指标结合起来,最终用一个八维向量来刻画蛋白质序列。为避免数据极差对分析结果造成的影响,本研究对蛋白质序列所对应的八维向量作归一化处理。基于归一化后的蛋白质序列的向量表示,运用神经网络对蛋白质序列进行分类,并根据向量之间的欧式距离来量化序列之间的相似性。最后,以9个不同物种的ND5蛋白质序列以及8个不同物种的ND6蛋白质序列为例,Clustal W序列比对方法为基准,对本研究的方法与5-字母方法进行验证和比较,结果表明本研的方法是有效的。  相似文献   

3.
蛋白质结构类预测是生物信息和蛋白质科学中重要的研究领域.基于Chou提出的伪氨基酸离散模型框架,从蛋白质序列出发,设计一种新的伪氨基酸组成方法表示蛋白质序列样本.抽取氨基酸组合(10-D)在序列中出现的频率和疏水氨基酸模式(6-D)表示蛋白质序列的附加特征,用和传统的氨基酸组成(20-D)一起构成的36维的伪氨基酸组成向量来表示蛋白质序列的特征.使用遗传算法来优化附加特征的权重系数.伪氨基酸组成向量作为输入数据,模糊支持向量机作为预测工具.使用三个常用的标准数据集来验证算法的性能.Jack-knife检验结果说明本方法具有较高的准确率,有望成为潜在的预测蛋白质功能的工具.  相似文献   

4.
在蛋白质结构预测的研究中,一个重要的问题就是正确预测二硫键的连接,二硫键的准确预测可以减少蛋白质构像的搜索空间,有利于蛋白质3D结构的预测,本文将预测二硫键的连接问题转化成对连接模式的分类问题,并成功地将支持向量机方法引入到预测工作中。通过对半胱氨酸局域序列连接模式的分类预测,可以由蛋白质的一级结构序列预测该蛋白质的二硫键的连接。结果表明蛋白质的二硫键的连接与半胱氨酸局域序列连接模式有重要联系,应用支持向量机方法对蛋白质结构的二硫键预测取得了良好的结果。  相似文献   

5.
基于支持向量机的蛋白质同源寡聚体分类研究   总被引:14,自引:1,他引:13  
基于支持向量机和贝叶斯方法,从蛋白质一级序列出发对蛋白质同源二聚体、同源三聚体、同源四聚体、同源六聚体进行分类研究,结果表明:基于支持向量机, 采用“一对多”和“一对一”策略, 其分类总精度分别为77.36%和93.43%, 分别比基于贝叶斯协方差判别法的分类总精度50.64%提高26.72和42.79个百分点.从而说明支持向量机可用于蛋白质同源寡聚体分类,且是一种非常有效的方法.对于多类蛋白质同源寡聚体分类,基于相同的机器学习方法(如支持向量机),采用“一对一”策略比“一对多”效果好.同时亦表明蛋白质同源寡聚体一级序列包含四级结构信息.  相似文献   

6.
给出了蛋白质序列的一种六维表示方法,根据这种表示方法有3种不同表示形式,利用这3种形式来构造距离矩阵的信息熵,然后通过信息熵向量的欧式距离、夹角来比较序列之间的相似性。  相似文献   

7.
基于蛋白质序列,提出了一种新的超二级结构模体β-发夹的预测方法。利用离散增量构成的向量来表示序列信息,并将6个离散增量输入支持向量机,在六维向量空间中寻找最优超平面,将β-发夹和非β-发夹进行分类。计算结果表明,利用所设计的算法预测β-发夹,有较高的预测能力。对于训练集,5-交叉检验的预测总精度为81.24%,相关系数为0.57,β-发夹敏感性为83.06%;对于独立的检验集,预测总精度为78.34%,相关系数0.56,β-发夹敏感性为77.24%。将此预测模型应用于CASP6的63个蛋白质进行检验,得到较好结果。  相似文献   

8.
蛋白质是生物体内最必需也是最通用的大分子,对它们功能的认识对于科学领域和农业领域的发展有着至关重要的作用。随着后基因组时代的发展,NCBI数据库中迅速涌现出大量不明结构与功能的蛋白质序列,这些蛋白质序列甚至一跃成了研究的热点。近几十年来蛋白质功能预测的方法不断被完善。由最初的仅基于蛋白质序列或3D结构信息的方法衍生出更多的基于序列相似性、基于结构基序、基于相互作用网络等新方法,这些新型方法采用新的算法、新的研究思路和技术手段,力求得到准确性与普遍性并存,能够被广泛应用的蛋白质功能预测方法。本文综述了近年来蛋白质功能预测的方法,并将这些研究方法分类归纳,各自阐明了每类方法的优缺点。  相似文献   

9.
基于多个结构域联合作用导致蛋白质间相互作用的假设,提出了一种预测蛋白质间相互作用的新方法。使用支持向量机分析结构域组合对序列的氨基酸理化性质得到其序列特征值,同时采用统计分析的方法获取其频率特征值,最后通过融合上述两种特征估计该结构域组合间发生相互作用的可能性,并以此预测蛋白质间相互作用关系。该方法能够预测所有结构域组合间相互作用关系,且对于蛋白质相互作用关系有着较好的预测效果。  相似文献   

10.
基于知识的蛋白质结构预测   总被引:5,自引:0,他引:5  
介绍了近几年基于知识的蛋白质三维结构预测方法及其进展.目前,基于知识的结构预测方法主要有两类,一类是同源蛋白模建,这种技术比较成熟,模建的结果可靠性比较高,但只适用于同源性比较高的目标序列的模建;另一类方法即蛋白质逆折叠技术,主要包括3D profile方法和基于势函数的方法,给出的是目标蛋白质的空间走向,它主要可用于序列同源性比较低的蛋白质的结构预测.  相似文献   

11.
Previous studies have demonstrated that 14-3-3 proteins exist in all the eukaryotic organisms studied; however, studies on the 14-3-3 proteins have not been involved in the halotolerant, unicellular green alga Dunaliella salina so far. In the present study, a cDNA encoding 14-3-3 protein of D. salina was cloned and sequenced by PCR and rapid amplification of cDNA end (RACE) technique based on homologous sequences of the 14-3-3 proteins found in other organisms. The cloned cDNA of 1485 bp in length had a 29.2 kDa of molecular weight and contained a 774 bp of open reading frame encoding a polypeptide of 258 amino acids. Like the other 14-3-3 proteins, the deduced amino acid sequences of the D. salina 14-3-3 protein also contained two putative phosphorylation sites within the N-terminal region (positions 62 and 67). Furthermore, an EF hand motif characteristic for Ca2+-binding sites was located within the C-terminal part of this polypeptide (positions 208–219). Analysis of bioinformatics revealed that the 14-3-3 protein of D. salina shared homology with that of other organisms. Real-time quantitative PCR demonstrated that expression of the 14-3-3 protein gene is cell cycle-dependent.  相似文献   

12.
There is increasing evidence that the vitamin D metabolite, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) has endocrine actions. In the current work, we report that an endogenous binding protein for 24,25(OH)2D3 is catalase, based on sequence analysis of the isolated protein. An antibody (Ab 365) generated against equivalent protein recognized bovine catalase and a 64 kDa band in subcellular fractions of chick intestine. A commercially available anti-catalase antibody reduced specific [3H]24,25(OH)2D3 binding in subcellular fractions of chick intestine by greater than 65%, relative to the same fractions treated with an unrelated antibody (Ab 099). The same commercially available anti-catalase was able to block the inhibitory actions of 24,25(OH)2D3 on 32P uptake in isolated intestinal epithelial cell suspensions. We subsequently characterized binding of steroid to commercially available catalase, and found that between 0 and 5 nM of enzyme added to subcellular fraction P2 (20,000g, 10-min post-nuclear pellet) resulted in a linear increase in the amount of [3H]24,25(OH)2D3 specifically bound. Additional studies indicated that 25(OH)D3 was an effective competitor for binding, whereas 1,25(OH)2D3 only poorly displaced [3H]24,25(OH)2D3. Saturation analyses with added catalase yielded a physiologically relevant affinity constant (KD=5.6+/-2.7 nM) and a Bmax=209+/-34 fmols/mg protein, comparable to previous studies using purified basal lateral membranes or vesicular fractions. Moreover, in a study on subcellular fractions isolated from chickens of varying ages, we found that in females, both specific [3H]24,25(OH)2D3 binding and catalase activity increased from 7- to 58-week-old birds, whereas in males, elevated levels of both parameters were expressed in preparations of 7- and 58-week-old birds. The data suggest that signal transduction may occur through modulation of hydrogen peroxide production.  相似文献   

13.
Weanling rats on a normal diet mobilized bone calcium in response to 11 daily injections of 125 ng of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)/100 g, body weight. This effect was most evident in the tibial midshaft, where calcium levels were reduced by 38% compared to untreated controls. Calcium levels were reduced by only 13% in the proximal tibial metaphysis, a region formed by longitudinal growth during the 11-day experiment. The concurrent daily administration of the vitamin K antagonist warfarin dramatically increased calcium mobilization from the tibial metaphysis of 1,25-(OH)2D3-treated rats. Compared to rats which received 1,25-(OH)2D3 alone, the calcium content of the tibial metaphysis in rats treated with 1,25-(OH)2D3 plus warfarin was reduced by 40.4% (p less than 0.001) and the total dry weight was reduced by 35.0% (p less than 0.001). There was no effect of warfarin on bone calcium content or dry weight in the absence of 1,25-(OH)2D3 treatment. These observations indicate that a component of the steroidal hormone action of 1,25-(OH)2D3 on bone may be mediated by increased synthesis of a vitamin K-dependent protein. The action of this vitamin K-dependent protein would oppose net calcium loss in the tibial metaphysis of 1,25-(OH)2D3-treated rats. This vitamin K-dependent protein may be the bone Gla protein, the only bone specific protein whose synthesis is known to be increased by 1,25-(OH)2D3.  相似文献   

14.
The dopamine β-hydroxylase (DβH) content and activity of large dense-core noradrenergic vesicles purified from bovine splenic nerve were determined using two assay procedures : enzymic activity expressed in Units per mg protein and homospecific activity based on radioimmunoassay expressed in Units per mg DβH antigen. Approximately two-thirds of the total enzyme activity is latent in these vesicles, even after various treatments designed to compromise vesicle integrity. DβH can be completely unmasked by brief treatment with 0.01-0.05% Triton X-100 and activity increases from 0.20 to 0.64 Units per mg vesicle protein. Calculations based on both assay methods suggested that an average of 7% (range 3-15%) of the total vesicle protein was DβH and that the average vesicle contained about 4 molecules of enzyme (range 2-9 molecules). The estimated homospecific activities indicated an average of 25 and 50% (range 18-72%) of the vesicle enzyme was inactive in the various samples using the two antibodies. The vesicle can synthesize up to 30 molecules of noradrenaline/s per molecule of DβH at near optimal substrate concentration, and 60-270 molecules of norepinephrine/s per vesicle. The assumptions used in the various calculations were critically analyzed and, based on the methods employed, it is tentatively considered to be unlikely that there could be more than 5-12 molecules of DβH per vesicle. The possibility that circulating DβH originates primarily, if not exclusively, from the large dense-core vesicle type is considered and the functional implications of the data support the concept of vesicle reuse during several cycles of exocytosis involving a quantal size equal to a fraction of the vesicle transmitter content.  相似文献   

15.
16.
The 14-3-3 epsilon protein was identified as one of the caspase-3 substrates by the modified yeast two-hybrid system. The cellular 14-3-3 epsilon protein was also cleaved in response to the treatment of apoptosis inducers in cultured mammalian cells. Asp238 of the 14-3-3 epsilon protein was determined as the site of cleavage by caspase-3. The affinity of the cleaved 14-3-3 mutant protein (D238) to Bad, a death-promoting Bcl-2 family protein, was lower than that of wild type or the uncleavable mutant 14-3-3 epsilon protein (D238A). However, Bad associated with the cellular Bcl-x(L) more effectively in human 293T cells co-expressing Bad with the truncated form of the 14-3-3 epsilon protein (D238) than in control cells co-expressing Bad with wild type or the uncleavable mutant 14-3-3 epsilon protein (D238A). The present study suggests that the cleavage of 14-3-3 protein during apoptosis promotes cell death by releasing the associated Bad from the 14-3-3 protein and facilitates Bad translocation to the mitochondria and its interaction with Bcl-x(L).  相似文献   

17.
1,25-(OH)2 vitamin D3 (1,25-(OH)2D3) exerts antiproliferative effects via cell cycle regulation in a variety of tumor cells, including prostate. We have previously shown that in the human prostate cancer cell line LN-CaP, 1,25-(OH)2D3 mediates an increase in cyclin-dependent kinase inhibitor p27Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G1. In this study, we investigated the mechanism whereby 1,25-(OH)2D3 increases p27 levels. 1,25-(OH)2D3 had no effect on p27 mRNA levels or on the regulation of a 3.5-kb fragment of the p27 promoter. The rate of p27 protein synthesis was not affected by 1,25-(OH)2D3 as measured by luciferase activity driven by the 5'- and 3'-untranslated regions of p27 that regulate p27 protein synthesis. Pulse-chase analysis of 35S-labeled p27 revealed an increased p27 protein half-life with 1,25-(OH)2D3 treatment. Because Cdk2-mediated phosphorylation of p27 at Thr187 targets p27 for Skp2-mediated degradation, we examined the phosphorylation status of p27 in 1,25-(OH)2D3-treated cells. 1,25-(OH)2D3 decreased levels of Thr187 phosphorylated p27, consistent with inhibition of Thr187 phosphorylation-dependent p27 degradation. In addition, 1,25-(OH)2D3 reduced Skp2 protein levels in LNCaP cells. Cdk2 is activated in the nucleus by Cdk-activating kinase through Thr160 phosphorylation and by cdc25A phosphatase via Thr14 and Tyr15 dephosphorylation. Interestingly, 1,25-(OH)2D3 decreased nuclear Cdk2 levels as assessed by subcellular fractionation and confocal microscopy. Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. These data suggest that Cdk2 mislocalization is central to the antiproliferative effects of 1,25-(OH)2D3.  相似文献   

18.
Electron spin echo envelope modulation (ESEEM) spectroscopy has been applied to the determination of the number of water molecules coordinated to the metal in the binary complex of staphylococcal nuclease with Mn2+, to the ternary enzyme-Mn2+-3',5'-pdTp complex, and to ternary complexes of a number of mutant enzymes in which metal-binding ligands have been individually altered. Quantitation of coordinated water is based on ESEEM spectral comparisons of Mn2+-EDTA and Mn2+-DTPA, which differ by a single inner sphere water, and with Mn2+-(H2O)6. It was found that Mn2+ in the ternary complex of the wild-type enzyme has a single additional coordinated water, as compared to Mn2+ in the binary complex, confirming earlier findings based on T1 measurements of bound water [Serpersu, E. H., Shortle, D. L., & Mildvan, A. S. (1987) Biochemistry 26, 1289-1300]. Ternary complexes of the mutant proteins D40E, D40G, and D21Y have the same number of water ligands as the ternary complex of the wild-type enzyme, while the D21E mutant has one less water ligand. In order to maintain octahedral coordination geometry, these findings require two additional ligands to Mn2+ from the protein in the binary complex of the wild-type enzyme, probably Glu 43 and Asp 19, and one additional ligand from the protein in the ternary D40G and D21E complexes. Other ESEEM studies of ternary Mn2+ complexes of wild-type, D21E, and D21Y mutants indicate the coordination by Mn2+ of a phosphate of 3',5'-pdTp, as demonstrated by a 31P contact interaction of 3.9 +/- 0.3 MHz. Magnetic interaction of Mn2+ with 31P could not be demonstrated with the D40G and D40E mutants, suggesting that metal-phosphate distances are greater in these mutants than in the wild-type protein. In a parallel NMR study of the paramagnetic effects of enzyme-bound Co2+ (which occupies the Mn2+ site on the enzyme) on the T1 of 31P from enzyme-bound 3',5'-pdTp and 5'-TMP, it was found that metal to 5'-phosphate distances are 0.9-1.6 A shorter in ternary complexes of the wild-type enzyme and of the D21E mutant than in ternary complexes of the D40G mutant. In all cases, the 5'-phosphate of pdTp is in the inner coordination sphere of Co2+ and the 3'-phosphate is predominantly in the second coordination sphere.  相似文献   

19.

Background  

Since many of the new protein structures delivered by high-throughput processes do not have any known function, there is a need for structure-based prediction of protein function. Protein 3D structures can be clustered according to their fold or secondary structures to produce classes of some functional significance. A recent alternative has been to detect specific 3D motifs which are often associated to active sites. Unfortunately, there are very few known 3D motifs, which are usually the result of a manual process, compared to the number of sequential motifs already known. In this paper, we report a method to automatically generate 3D motifs of protein structure binding sites based on consensus atom positions and evaluate it on a set of adenine based ligands.  相似文献   

20.
We have developed an assay to measure the affinity of serum vitamin D binding protein for 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and vitamin D3, using uniform diameter (6.4 microns) polystyrene beads coated with phosphatidylcholine and vitamin D metabolites as the vitamin D donor. The lipid metabolite coated beads have a solid core, and thus all of the vitamin D metabolites are on the bead surface from which transfer to protein occurs. After incubating these beads in neutral buffer for 3 h, essentially no 3H-labeled vitamin D metabolites desorb from this surface. Phosphatidylcholine/vitamin D metabolite-coated beads (1 microM vitamin D metabolite) were incubated with varying concentrations of serum vitamin D binding protein under conditions in which the bead surfaces were saturated with protein, but most of the protein was free in solution. After incubation, beads were rapidly centrifuged without disturbing the equilibrium of binding and vitamin D metabolite bound to sDBP in solution was assayed in the supernatant. All three vitamin D metabolites became bound to serum vitamin D binding protein, and after 10 min of incubation the transfer of the metabolites to serum vitamin D binding protein was time independent. The transfer followed a Langmuir isotherm, and the Kd for each metabolite binding to serum vitamin D binding protein was derived by nonlinear least-squares fit analysis. From this analysis the following values for the Kd were obtained: 5.59 x 10(-6) M, 25-hydroxyvitamin D; 9.45 x 10(-6) M, 1,25-dihydroxyvitamin D; and 9.17 x 10(-5) M, vitamin D. In conclusion, we have developed a method which avoids problems encountered in previous assays and allows the precise and convenient determination of binding affinities of vitamin D metabolites and serum vitamin D binding protein.  相似文献   

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