SUBTLE SEQUENCE PATTERNS IN DNA-BINDING COMPLEXES

识别特定序列的蛋白质种类的数量， DNA的结构正在快速增长。 有几个很大 几种类型的亚基的复合物。在这个项目中，计算 目前正在开发识别一些功能性氨基酸的策略， 酸序列模式，其中许多是微妙的和可变的。 改进的方法正被应用于新序列的分析 在其他NIH实验室确定，导致新的见解 重要基因产物的分子结构和功能。为 已确立的DNA结合区模式，如螺旋-转角-螺旋 和基本区域，新的诊断能力的评价方法， 模式鉴别器正在被开发并应用于更新颖的 模式. 低复杂性序列在DNA结合蛋白中很常见 并且在数据库搜索之前需要分析和过滤。 吉布斯 一种通过迭代采样的自动局部多重比对方法， 也包括在这些战略中。 各种类型的DNA测试集- 结合基序已经被明智地构建用于评估这一点， 和相关方法。分析的特异性序列包括（1）127 kDa 紫外线损伤的DNA结合复合物的组成部分，这是有缺陷的，在一些 着色性干皮病E组患者和显示序列相似性 对来自广泛的真核生物的未知功能的蛋白质，（2）六个 转录因子TFIID复合物的亚基，其在 通过促进启动子对多种转录因子的应答来进行转录调控 激活剂，和（3）DNA修复酶的各种家族。

The number of classes of proteins that recognize specific sequences and structures of DNA is continuing to grow rapidly. Several are large complexes of several types of subunit. In this project, computational strategies are being developed to recognize some of the functional amino acid sequence patterns involved, many of which are subtle and variable. Improved methods are being applied to the analysis of new sequences determined in other NIH laboratories, resulting in new insights into the molecular structures and functions of important gene products. For patterns of well-established DNA binding regions such as helix-turn-helix and basic regions, new methods for evaluation of the diagnostic power of pattern discriminators are being developed and applied to more novel patterns. Low-complexity sequences are frequent in DNA-binding proteins and require analysis and filtering before database searches. The gibbs method of automated local multiple alignment by iterative sampling is also included in these strategies. Test sets of various types of DNA- binding motifs have been judiciously constructed for evaluation of this and related methods. Specific sequences analyzed include (1) 127 kDa component of a UV-damaged-DNA binding complex, which is defective in some Xeroderma pigmentosum Group E patients and shows sequence similarities to proteins of unknown function from a wide range of eukaryotes, (2) six subunits of the transcription factor TFIID complex that is central in transcriptional regulation by facilitating promoter responses to various activators, and (3) various families of DNA repair enzymes.