MULTI-SCALE VISUALIZATION OF LARGE MOLECULAR COMPLEXES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们正在开发UCSF嵌合体分子的软件扩展， 交互式建模软件包（http：//www.cgl.ucsf.edu/chimera） 可视化和分析大型分子组件， 病毒和核糖体。 这些扩展有助于研究原子 分辨率模型在一个范围内的尺度从原子细节， 二级结构（螺旋和片层）到三级结构 （蛋白质和核酸折叠），四级结构（包装的 大分子以形成组装体）。 虽然许多计算机程序 允许交互式探索蛋白质或核酸的小集合 大分子，没有一个能很好地与30个或更多的组件一起工作 分子。 已知的病毒颗粒结构由数百个 成千上万的分子，特别难以研究 现有软件。 我们开发的软件主要针对四级结构水平。 基本功能封装在多尺度模型工具中。 它允许将分子表示为简单的表面， 分子形状 这种抽象对于具有以下特性的系统是必要的： 数百个分子。 运用对称性是另一个基本能力。 约250个病毒衣壳结构中的大多数具有二十面体 对称性 仅指定不对称单位（衣壳的1/60） 在原子坐标文件中。 我们可以利用对称性 显示整个衣壳，而只创建原子的副本 当需要显示不对称单位时， 不同的风格和颜色。 这对病毒衣壳很重要 可以包含数百万个原子。 除了抽象 表示和对称处理，这是 大型装配在导航到相关的装配中。 为 例如，病毒衣壳可以具有两层，每层由数百个 蛋白质。 需要一种机制来隐藏外层， 可以研究内层。 病毒壳体等亚组装体 蛋白质数据库文件中一般不对图层进行注释， 由用户来定义这些参数。 我们的多尺度 扩展允许使用用户定义的 分子分组。 多尺度模型工具的详细信息发表在戈达德TD， 黄CC，费林TE。 UCSF嵌合体的软件扩展， 大型分子组装体的交互式可视化。结构 （坎布）。2005年3月;13（3）：473-82。 在过去几年中增加的更先进的功能包括一个高效的 计算分子间原子接触的算法 组件，显示晶体晶胞的能力， 能够删除组件，能够显示透明表面 与其他分子显示样式结合， 导出制作动画的三维模型。 这些功能已用于创建病毒粒子的图像 资源管理器网站（http：//viperdb.scripps.edu/）， 二十面体病毒衣壳结构。

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. We are developing software extensions to the UCSF Chimera molecular modeling package (http://www.cgl.ucsf.edu/chimera) for interactive visualization and analysis of large molecular assemblies such as viruses and ribosomes. These extensions facilitate studying atomic resolution models over a range of scales from atomic detail, to secondary structure (helices and sheets), to tertiary structure (protein and nucleic acid folds), to quaternary structure (packing of macromolecules to form an assembly). While many computer programs permit interactive exploration of small sets of protein or nucleic acid macromolecules, none work well with assemblies of 30 or more molecules. Known virus particle structures are composed of hundreds to thousands of molecules and are particularly difficult to study with existing software. The software we've developed focus on the quaternary structure level. The basic capabilities are encapsulated in the Multiscale Models tool. It allows representing molecules as simple surfaces that show overall molecular shape. This abstraction is needed for systems having hundreds of molecules. Applying symmetry is another basic capability. Most of the approximately 250 virus capsid structure have icosahedral symmetry. Only the asymmetric unit (1/60 of the capsid) is specified in atomic coordinate files. We are able to use the symmetry to display the entire capsid while only creating copies of the atomic coordinates when they are needed for displaying asymmetric units with differing styles and colorings. This is important for virus capsids which can contain millions atoms. In addition to abstract representations and symmetry handling, another challenge posed by large assemblies is in navigating to relevant subassemblies. For example, a virus capsid may have two layers each comprised of hundreds of proteins. A mechanism is needed to hide the outer layer so that the inner layer can be studied. Subassemblies such as virus capsid layers are in general not annotated in the Protein Databank files so defining these subassemblies is left to the user. Our multiscale extension permits navigating to subassemblies using user-defined molecule groupings. Details of the Multiscale Models tool were published in Goddard TD, Huang CC, Ferrin TE. Software extensions to UCSF chimera for interactive visualization of large molecular assemblies. Structure (Camb). 2005 Mar;13(3):473-82. More advanced capabilites added in past years include an efficient algorithm for calculating atomic contacts between molecular components, the ability to show crystallographic unit cells, the ability to delete components, the ability to show transparent surfaces in combination with other molecular display styles, and ability to export 3 dimensional models for making animations. These capabilities have been used to create images for Virus Particle Explorer web site (http://viperdb.scripps.edu/) for all known icosahedral virus capsid structures.