Molecular

项目总结(见说明)： 分子建模设备(MMF)在蛋白质序列分析中提供最先进的服务 和结构预测提供给狐狸大通癌症中心(Fccc)的研究人员。这些服务包括数据库搜索、多序列比对、系统发育树比较、二级结构预测、跨膜、卷曲和无序区预测、单个蛋白质和复合体的同源性建模、蛋白质-蛋白质和蛋白质-配体对接，以及配基设计。 该机制自2003年以来一直在运作，并在上次审查中被批准为CCSG资源。 目前，至少一半的测序蛋白质至少部分与已知结构的蛋白质同源。同源建模方法利用已知结构构建目标蛋白质的三维模型和未知结构的蛋白质复合体。这些模型可以用来预测与其他分子的功能相互作用，解释现有的实验数据，产生可检验的假说， 并在某些情况下成为设计转化性研究的特定抑制剂的基础。自2005年以来，该基金在所有五个研究方案中为48名首席调查人员提供了服务，并提供了同行审查的资金。设施和设施主任的研究小组开发了用于自动建模过程的新软件，使设施工作人员有更多时间专注于生物 正在研究中的问题。特别是，他们开发了预测蛋白质同源和异质低聚物结构的方法，这些低聚物包含许多重要的功能相互作用。该软件是可扩展的，因此当新工具可用时，它允许将它们合并到相同的图形用户界面中。 随着双杂交相互作用图谱和双向凝胶电泳等技术允许研究人员识别更多蛋白质的功能和物理相互作用，对详细结构信息的需求将迅速增长。因此，预计这一机制的使用在今后五年中将大幅增长。该基金的服务将为了解复杂的生物系统提供越来越重要的信息。

PROJECT SUMMARY (See instructions): The Molecular Modeling Facility (MMF) provides state-of-the-art services in protein sequence analysis and structure prediction to Fox Chase Cancer Center (FCCC) investigators. These services include database searches, multiple sequence alignments, phylogenetic tree comparisons, secondary structure predictions, transmembrane, coiled-coil and disordered region predictions, homology modeling of single proteins and complexes, protein-protein and protein-ligand docking, and ligand design. The Facility has been operating since 2003, and was approved as a CCSG resource at the last review. Currently, at least one-half of sequenced proteins are homologous at least in part to a protein of known structure. Homology modeling methods use known structures to build three-dimensional models of target proteins and protein complexes of unknown structure. These models can be used to predict functional interactions with other molecules, to explain existing experimental data, to generate testable hypotheses, and in some cases to become the basis for design of specific inhibitors for translational research. The Facility has performed services for 48 principal investigators with peer-reviewed funding in all five Research Programs since 2005. The Facility and the Facility Director's research group have developed new software for automating the modeling process to allow Facility staff more time to concentrate on the biological problem under study. In particular, they have developed methods for predicting the structures of protein homo- and heterooligomers, which comprise many important functional interactions. This software is extensible, so that it allows new tools to be incorporated into the same graphical user interface as they become available. As technologies such as two-hybrid interaction mapping and two-dimensional gel electrophoresis allow investigators to identify functional and physical Interactions of larger numbers of proteins, the demand for detailed structural information will grow rapidly. The use of this Facility is therefore expected to grow significantly over the next five years. The services of the Facility will provide increasingly important information for understanding complex biological systems.