CORE--MOLECULAR MODELING FACILITY

分子模拟设施提供蛋白质序列分析的最先进的服务 福克斯大通癌症中心（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、二级结构预测、跨膜、卷曲螺旋和无序区域预测、单个蛋白质和复合物的同源性建模、蛋白质-蛋白质和蛋白质-配体对接以及配体设计。这是CCSG续期申请中的一项新贷款。目前，三分之一到二分之一的测序蛋白质与已知结构的蛋白质至少部分同源。同源建模方法使用已知的结构来构建未知结构的靶蛋白的三维模型。这些模型可用于预测与其他分子的功能相互作用，解释现有的实验数据，生成可验证的假设，并在某些情况下成为设计用于转化研究的特定抑制剂的基础。该基金成立于2003年4月，自那时以来，已为八个研究项目和FCCC所有三个部门的15名主要研究人员提供了同行评审资金服务。该设施还开发了新的软件，使建模过程自动化，使设施工作人员有更多的时间与主要研究人员合作，集中精力研究生物学问题。该软件是可扩展的，因此它允许 新的工具将被纳入同一图形用户界面，因为他们成为可用。 随着双杂交相互作用作图和二维凝胶等新技术的发展， 随着电泳技术的发展，研究人员可以在完全测序的基因组中识别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，预计在今后五年内，该基金的使用将大幅增加。该设施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.