CORE--MOLECULAR MODELING FACILITY

分子建模设备提供最先进的蛋白质序列分析服务 福克斯·蔡斯癌症中心研究人员对干旱结构的预测。这些服务包括数据库搜索、多序列比对、系统发育树、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-配体对接以及配体设计。这是CCSG此次续签申请中的一项新设施。目前，测序的蛋白质中有三分之一到一半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来构建未知结构的靶蛋白质的三维模型。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，在某些情况下成为设计特定抑制剂的基础，用于翻译研究。该机制成立于2003年4月，自那时以来，已向15名首席调查员提供了服务，并在八个研究方案和联合国气候变化框架公约的所有三个司提供了同行审查资金。该基金还开发了新的软件，使建模过程自动化，使该基金的工作人员有更多时间与首席调查员合作，集中精力研究正在研究的生物问题。这个软件是可扩展的，所以它允许 新工具将整合到相同的图形用户界面，因为它们是可用的。 作为双杂交相互作用图谱和二维凝胶等新技术 电泳法使研究人员能够识别全序列基因组中大量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。

The Molecular Modeling Facility provides state-of-the-art services in protein sequence analysis arid structure prediction to Fox Chase Cancer Center (FCCC) investigators. These services include database search, multiple sequence alignment, phylogenetic trees, secondary structure prediction, transmembrane, coiled-coil and disordered region prediction, homology modeling of single proteins and complexes, protein-protein and protein-ligand docking, and ligand design. This is a new Facility in this renewal application of the CCSG. Currently, one-third to 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 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 was created in April 2003, and since that time has performed services for 15 principal investigators with peer-reviewed funding in eight Research Programs and all three Divisions of FCCC. The Facility has also developed new software for automating the modeling process to allow Facility staff more time to concentrate on the biological problem under study in collaboration with the principal investigator. This software is extensible, so that it allows new tools to be incorporated into the same graphical user interface as they become available. As new 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 in fully sequenced genomes, 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.