CHIMERA EXTENSIONS FOR IMP

IMP 的嵌合体延伸

• 批准号: 8363631
• 负责人: THOMAS E FERRIN
• 金额: $ 2.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363631
• 关键词: Algorithms; Area; Chimera organism; Cryoelectron Microscopy; Data; Feedback; Funding; Grant; Graph; Imagery; Individual; Informatics; Manuals; Maps; Modeling; Modification; National Center for Research Resources; Positioning Attribute; Principal Investigator; Process; Proteins; Proteomics; Relative (related person); Research; Research Infrastructure; Resources; Roentgen Rays; Running; Source; Structure; Torsion; United States National Institutes of Health; biocomputing; comparative; cost; density; process optimization; programs; protein complex; restraint; three dimensional structure; web services

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In conjunction with Prof. Andrej Sali's group at UCSF, we will implement Chimera extensions and web services to support protein and protein complex modeling in three main areas: 1) Comparative modeling and loop modeling of individual proteins. Specifically, we will take the algorithms implemented as part of the widely used comparative modeling program Modeller, and make them available as a web service. We will then enhance Chimera so that a user providing a sequence to be modeled and a structure to be used as the template could use this web service to produce a model. 2) Determination of the structures of large assemblies using cryoEM and proteomics data. We will use Chimera to view and guide the process of determining the structures of large assemblies with IMP using cryoEM and proteomics data. The user will be able to view and refine models at intermediate steps of the optimization process. Chimera will be used to display the density map and an anchor graph, which shows the approximate positions of protein centroids in the assembly and the interactions among them. The anchor graph is calculated by the MultiFit. We will support the following ways of interacting with the MultiFit process: 1) manual positioning and orientating of the proteins in the density guided by the anchor graph and then calling MultiFit for local refinement; 2) manual positioning of proteins on anchor points but using MultiFit to search all possible orientations; 3) manual positioning and orientating of proteins within the assembly model guided by dynamic feedback of the individual restraint values and overall score from MultiFit; and 4) running MultiFit without any initial positioning but allowing manual refinement at intermediate steps as described above. 3) Structural refinement and fitting using Small Angle X-Ray Scattering (SAXS) data. We will support the use of experimental and computed SAXS profiles to guide the modification and refinement of modeled structures. The following ways of combining 3D structure and SAXS profiles will be implemented: 1) loading a structure and SAXS profile simultaneously and displaying them together; 2) computing and displaying the SAXS profile for part or all of the displayed structure; 3) fitting the computational SAXS profile to the experimental one and displaying them together; 4) recalculating the SAXS profile automatically as the structure is interactively modified (for example, by changing torsion angles or moving proteins relative to each other); and 5) refining the assembly model to better fit the experimental SAXS profile using an IMP web service.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 与UCSF的安德烈·萨利（Andrej Sali）教授的小组一起，我们将实施嵌合体扩展和Web服务，以支持三个主要领域的蛋白质和蛋白质复杂建模： 1）单个蛋白质的比较建模和循环建模。 具体而言，我们将将实施的算法作为广泛使用的一部分 比较建模程序模型器，并将其作为Web服务提供。然后，我们将增强Chimera，以便提供要建模的序列的用户，并使用该模板使用此Web服务来生成模型的结构。 2）使用冷冻和蛋白质组学数据确定大型组合的结构。 我们将使用Chimera使用Cryoem和蛋白质组学数据来查看和指导通过IMP确定大型组合的结构的过程。用户将能够在优化过程的中间步骤中查看和完善模型。嵌合体将用于显示密度图和锚图，该图显示了蛋白质质心在组件中的近似位置以及它们之间的相互作用。锚图由多率计算。我们将支持以下方式与多重过程相互作用的方法：1）在锚图指导下的密度中手动定位和定向蛋白质，然后呼吁多进化以进行局部细化； 2）蛋白质在锚点上的手动定位，但使用多率来搜索所有可能的方向； 3）在组装模型中，手动定位和定向蛋白质在单个约束值的动态反馈和从多率的总体得分的指导下； 4）在没有任何初始定位的情况下运行多率，但如上所述，可以在中间步骤进行手动细化。 3）使用小角度X射线散射（SAXS）数据进行结构改进和拟合。 我们将支持使用实验和计算的SAXS轮廓来指导建模结构的修改和完善。结合3D结构和SAXS配置文件的以下方法将实现：1）同时加载结构和SAXS配置文件并将它们显示在一起； 2）计算和显示部分或所有显示结构的SAXS配置文件； 3）将计算SAXS配置文件拟合到实验中并将其显示在一起； 4）重新计算SAXS配置文件 自动随着结构进行交互修改（例如，通过更改扭转角或移动蛋白质相对于彼此而言）； 5）完善组装模型以更好地拟合实验的SAXS曲线 使用IMP Web服务。