Rosetta: An Integrated Macromolecular Modeling Suite

描述（由申请人提供）：Rosetta是为预测和设计大分子结构而开发的分子建模软件。Rosetta在蛋白质结构预测和对接的社区范围内的评估中表现良好，它已被用于设计新的蛋白质结构，以及设计改变特异性的蛋白质-蛋白质和蛋白质- dna相互作用。Rosetta由11所独立大学的研究小组开发和维护，超过2400个实验室获得了该软件的免费许可证。2004年之前，Rosetta是用Fortran 77编写的。在过去的三年里，我们利用NIH的支持创建了一个新的面向对象的c++版本的Rosetta。新软件被组织为一组库，其中包含类和例程，用于表示和评分分子系统，用于持有移动集，并用于执行大分子构象和序列的优化。本建议的主要目标是利用这次重写，并在代码不是模块化和面向对象时不太可行的方向上扩展Rosetta软件。目前，Rosetta通过命令行界面运行，强制用户从一组固定的建模协议中进行选择，例如蛋白质-蛋白质对接或蛋白质单体的设计。我们将在Rosetta中创建一个框架，允许用户使用c++或脚本语言Python轻松创建自定义协议。python绑定将用于创建PyMOL的接口，PyMOL是一个广泛使用的分子可视化程序。这将为启动和与罗塞塔模拟交互以及快速评估罗塞塔模型的质量提供图形界面。Rosetta的大多数应用都受益于增加的构象和/或序列空间采样，因此受益于更快的算法。我们将利用新的c++对象来缓存能量，从而提高Rosetta的计算速度。这笔拨款还将通过维护测试代码完整性的基准、维护用户指南和支持不同机构的开发人员之间的会议来支持开发人员和用户。公共卫生相关性：蛋白质、RNA或DNA分子的功能在很大程度上取决于其三维结构。我们的目标是开发一个最先进的计算机程序来预测和设计生物大分子的结构。该项目将免费提供给学术实验室，其预测将帮助研究人员了解和对抗癌症和艾滋病等人类疾病。

DESCRIPTION (provided by applicant): Rosetta is molecular modeling software that has been developed for the prediction and design of macromolecular structure. Rosetta has performed well in community wide assessments of protein structure prediction and docking, and it has been used to design new protein structures as well as design altered specificity protein-protein and protein-DNA interactions. Rosetta is developed and maintained by research groups at 11 separate universities, and over 2400 laboratories have obtained free licenses for the software. Until 2004, Rosetta was written in Fortran 77. Over the past three years we have used NIH support to create a new C++ object-oriented version of Rosetta. The new software is organized as a set of libraries that contain classes and routines for representing and scoring molecular systems, for holding move sets, and for performing optimization of macromolecular conformation and sequence. The primary goal of this proposal is to capitalize on this rewrite, and extend the Rosetta software in directions that were less feasible when the code was not modular and object-oriented. Currently, Rosetta runs through a command line interface that forces users to choose from a fixed set of modeling protocols, such as protein-protein docking or the design of protein monomers. We will create a framework within Rosetta that allows users to easily create custom protocols in either C++ or with the scripting language Python. The python binding will be used to create an interface with PyMOL, a widely used program for molecular visualization. This will provide a graphical interface for initiating and interacting with Rosetta simulations as well as rapidly evaluating the quality of Rosetta models. Most applications of Rosetta benefit significantly from increased sampling of conformational and/or sequence space, and therefore, benefit from faster algorithms. We will increase the speed of Rosetta calculations by taking advantage of new C++ objects for caching energies. This grant will also support developers and users by maintaining benchmarks that test the integrity of the code, maintaining the user's guide and supporting meetings between developers at the various institutions. PUBLIC HEALTH RELEVANCE: The function of a protein, RNA or DNA molecule is largely determined by its 3- dimensional structure. We aim to develop a state-of-the-art computer program for predicting and designing the structures of biological macromolecules. The program will be freely available to academic laboratories and its predictions will help investigators understand and fight human diseases such as cancer and AIDS.