ROSETTA An Integrated Protein Structure Modeling Suite

描述(由申请人提供)： 这项提议的目的是使用于蛋白质结构建模的Rosetta软件包现代化，以促进其在多个研究小组中继续并行开发，并促进该软件在科学界的广泛使用。实现这一目标将对计算结构生物学产生非常广泛的积极影响，因为在许多关键领域，Rosetta方法似乎至少与其他方法一样好，甚至更好。通过促进整个科学界一大批研究人员对该软件的进一步开发和应用，该软件的功能和用途应该会大大增加。Rosetta目前包含从头蛋白质结构预测、蛋白质设计、蛋白质-蛋白质对接、蛋白质和蛋白质DNA接口设计、蛋白质-蛋白质和蛋白质-DNA相互作用专一性预测、环路建模和高分辨率蛋白质结构优化的模块。这些不同的应用程序为所有模块共享的底层潜在功能和优化方法提供了严格的测试，刺激了这两个领域的持续改进。当这些改进的核心元素被结合到集成的Rosetta结构建模平台中时，所有单独的应用程序都会受益。通过允许组合多个模块来解决复杂的建模问题，在单个包中集成不同的模块使得实质性的进步成为可能。例如，结合使用结构预测、蛋白质设计和模型优化模块，可以设计出具有原子级精度的新型蛋白质折叠。为了促进不同模块的进一步集成，以解决灵活的主干蛋白质-蛋白质对接等问题，并促进新特性和功能的继续开发，Rosetta包将移植到C++并现代化到面向对象的设计。为了促进该软件的广泛使用，将开发一个全面的Rosetta网络服务器，将向科学界免费提供现代化的源代码和广泛的文件，并鼓励整个社区的研究人员加入日益壮大的Rosetta开发团队。

DESCRIPTION (provided by applicant): The aim of this proposal is to modernize the Rosetta software package for protein structure modeling in order to facilitate its continued development in parallel in multiple research groups and to promote the widespread use of the software in the scientific community. Achieving this aim would have a very positive impact on computational structural biology quite broadly because in many critical areas, the Rosetta methodology appears to be at least as good, if not better, than other approaches. By facilitating further development and application of the software by a large group of researchers throughout the scientific community, the power and usefulness of the software should increase enormously. Rosetta currently contains modules for de novo protein structure prediction, protein design, protein-protein docking, proteinprotein and proteim DNA interface design, protein-protein and protein-DNA interaction specificity prediction, loop modeling, and high-resolution protein structure refinement. These diverse applications provide stringent tests for the underlying potential functions and optimization methods that are shared by all modules, stimulating continued improvements in both areas. When such improved core elements are incorporated into the integrated Rosetta structure-modeling platform, all the individual applications reap the benefits. Integration of the different modules in a single package has made substantial advances possible by allowing multiple modules to be combined to address complex modeling problem. For example, the combined use of the structure prediction, protein design, and model refinement modules allowed the design of a novel protein fold with atomic level accuracy. To facilitate further integration of the different modules to attack problems such as flexible backbone protein-protein docking, and to facilitate the continued development of new features and functionality, the Rosetta package will be ported to C++ and modernized to an object-oriented design. To promote widespread use of the software, a comprehensive Rosetta web server will be developed, the modernized source code will be made freely available to the scientific community with extensive documentation, and researchers throughout the community will be encouraged to join the growing Rosetta development team.