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基于启动子的以下特点:(1)启动子区域有一些一致序列,但对于不同的启动子,一致序列在个别碱基上会有所改变,具有多样性;(2)一致序列的位置并不固定,总是在某个范围内波动;(3)大部分的真核生物启动子都和CpG岛有关。提出了一个新的启动子预测方法,即采用了一种新的统计建模策略,并首次提出了区间位置权重矩阵(IPWM)概率模型。大规模序列测试结果表明,新的启动子预测系统具有较好的敏感性和特异性。  相似文献
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Protein-protein recognition, frequently mediated by members of large families of interaction domains, is one of the cornerstones of biological function. Here, we present a computational, structure-based method to predict the sequence space of peptides recognized by PDZ domains, one of the largest families of recognition proteins. As a test set, we use a considerable amount of recent phage display data that describe the peptide recognition preferences for 169 naturally occurring and engineered PDZ domains. For both wild-type PDZ domains and single point mutants, we find that 70-80% of the most frequently observed amino acids by phage display are predicted within the top five ranked amino acids. Phage display frequently identified recognition preferences for amino acids different from those present in the original crystal structure. Notably, in about half of these cases, our algorithm correctly captures these preferences, indicating that it can predict mutations that increase binding affinity relative to the starting structure. We also find that we can computationally recapitulate specificity changes upon mutation, a key test for successful forward design of protein-protein interface specificity. Across all evaluated data sets, we find that incorporation backbone sampling improves accuracy substantially, irrespective of using a crystal or NMR structure as the starting conformation. Finally, we report successful prediction of several amino acid specificity changes from blind tests in the DREAM4 peptide recognition domain specificity prediction challenge. Because the foundational methods developed here are structure based, these results suggest that the approach can be more generally applied to specificity prediction and redesign of other protein-protein interfaces that have structural information but lack phage display data.  相似文献
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基于已知的人类PolII启动子序列数据,综合选取启动子序列内容和序列信号特征,构建启动子的支持向量机分类器.分别以启动子序列的6-mer频数作为离散源参数构建序列内容特征。同时选取24个位点的3-mer频数作为序列信号特征构建PWM,将所得到的两类参数输入支持向量机对人类启动子进行预测.用10折叠交叉检验和独立数据集来衡量算法的预测能力,相关系数指标达到95%以上,结果显示结合了支持向量机的离散增量算法能够有效的提高预测成功率,是进行真核生物启动子预测的一种很有效的方法.  相似文献
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The choice of a splice site is not only related to its own intrinsic strength, but also is influenced by its flanking competitors. Splice site competition is an important mechanism for splice site prediction, especially, it is a new insight for alternative splice site prediction. In this paper, the position weight matrix scoring function is used to represent splice site strength, and the mechanism of splice site competition is described by only one parameter: scoring function subtraction. While applying on the alternative splice site prediction, based on the only one parameter, 68.22% of donor sites and 70.86% of acceptor sites are correctly classified into alternative and constitutive. The prediction abilities are approximately equal to the recent method which is based on the mechanism of splice site competition. The results reveal that the scoring function subtraction is the best parameter to describe the mechanism of splice sites competition.  相似文献
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