COMPUTATIONAL BIOCHEMISTRY

蛋白质家族和序列基序的鉴定是 随着人类基因组序列信息的重要性日益增加， 项目开始可用。 在早期的工作中， 奖，我们开发了一种计算基于序列的基序的技术 描述或进化概况（EP）。 简单地说，这种方法适用于 一个明确的进化模型，每个对齐的位置，在一组 对齐的序列。 这个模型描述了最好的进化 20个氨基酸残基中每一个的距离。 有限混合物 然后计算模型，其中20个可能的 祖先残基通过其产生以下结果的概率来加权： 在给定的进化距离上观察到的分布。 在 今年继续工作，我们正在使用EP方法构建 丝氨酸/苏氨酸和酪氨酸激酶的整个家族的模型。 该项目涉及建设多个路线， 5个主要激酶家族和55个亚家族， 下一代EP EP是有效的描述/分类器 对于蛋白质家族，激酶谱将用于分类 新的激酶，并提供蛋白质的多重序列比对 在SDSC的激酶资源。 不断改进轮廓分析 方法是从软件的这种“试验台”使用中产生的。 基于 根据去年的经验，我们实施了一项新的 用于模式识别的灵活服务器。 这个服务器，SeqWeb， 旨在支持多种模式的多种应用程序， 互动 通过互联网提供最终用户应用程序， 各种困难。 虽然有些申请可以在 时间短，因此是提供 通过交互式网页提供服务，其他服务则需要数分钟或数小时 因此必须采用不同的交互模式。 此外，许多应用程序需要来自其他程序的输入，或者 为其他程序提供输入。 对于传统的交互式 服务器，这需要频繁地将数据复制到服务器和从服务器复制数据; 每个步骤都容易出错并增加出错的机会。 的 SeqWeb服务器旨在解决其中的许多问题。 提供临时文件存储以便于使用系列 的程序。 本地文件存储还允许系统 严格控制文件的格式，避免了许多繁琐的格式 转换和文件传输引入的错误。 这也 为分析提供了一个取放交互， 需要几分钟以上。 此外，SeqWeb还提供了 通过网页（传统模式）和电子邮件返回结果 （类似于MEME/MAST服务器）。 这三种互动模式 在提供访问方面提供了极大的增强灵活性， 应用. SeqWeb的当前版本实现了一系列 与上述进化概况方法一起使用的程序： 具体地，多序列比对、序列加权、概况分析 创建、配置文件数据库搜索（使用Bioccelerator），以及 序列和图谱的比对。 SeqWeb还提供访问 本地可用的数据库，以及用于自定义显示 对齐。 明年，SeqWeb将扩展到包括 与NBCR合作开发的MEME和MAST计划，以及 通过添加其他显示和分析功能进行扩展 功能协调发展的

Identification of protein families and the sequence motifs is increasingly important as sequence information from the Human Genome Project begins to be available. In earlier work supported by this award, we developed a technique for calculating sequence based motif descriptions or evolutionary profiles (EP). Briefly, this method fits an explicit evolutionary model to each aligned position in a group of aligned sequences. This model describes the best evolutionary distance for each of the twenty amino acid residues. A finite mixture model is then calculated in which each of the twenty possible ancestral residues is weighted by its probability of giving rise to the observed distribution at the given evolutionary distance. In continuing work this year we are using the EP method to construct models for the entire family of serine/threonine and tyrosine kinases. This project involves the construction of multiple alignments for each of the five major kinase families and 55 subfamilies, and the subsequent generation of EP. EP are effective description/classifiers for protein families, and the kinase profiles will be used to classify novel kinases and provide multiple sequence alignments for the Protein Kinase Resource at SDSC. Continual improvements to profile analysis methods are resulting from this "testbed" use of the software. Based on experience from the last year we have implemented a new and more flexible server for pattern recognition. This server, SeqWeb, is designed to support multiple application in a variety of modes of interaction. Providing end-user applications via the internet poses a variety of difficulties. While some applications can be completed in short periods of time, and thus are good candidates for providing services via an interactive web page, others require minutes or hours to finish and must therefore employ a different interactive mode. Furthermore, many applications require inputs from other programs, or provide inputs to other programs. For a traditional interactive server, this requires frequent copying of data to and from the server; each step is error prone and increases the chance of errors. The SeqWeb server has been designed to address many of these issues. Temporary file storage is provided to facilitate the use of a series of programs. Local file storage also allows the system to more closely control the format of files, and obviates many tedious format conversions and errors introduced by file transfers. This also provides for a drop-off and pick-up interaction for analyses that require more than a few minutes. In addition, SeqWeb provides for the return of results by web pages (traditional mode) and by email (similarly to the MEME/MAST server). These three modes of interaction provide greatly enhance flexibility in provided access to applications. The current version of SeqWeb implements a series of programs for use with the evolutionary profile method described above: specifically, multiple sequence alignment, sequence weighting, profile creation, profile database searching (using Bioccelerator), and alignment of sequences and profiles. SeqWeb also provides ac cess to databases available locally, and tools for the custom display of alignments. In the next year SeqWeb will be extended to include the MEME and MAST programs developed in collaboration with NBCR, and its functionality extended by the addition of other display and analysis functions.