Predoctoral Fellowships for Students with Disabilities

描述(由申请人提供)：该项目的长期目标是通过修改新的结构改进技术(已开发并被证明对晶体结构有效)来更好地了解并改进大分子的结构表征和精炼过程，以应用于核磁共振(核磁共振)结构。无论哪种方法，更准确、更详细的结构都将有助于理解生物功能，并有助于在许多医学应用中进行药物设计和蛋白质设计工作。将采用的方法是使用实时可更新的可视化，该可视化强调与当前局部模型相比，核磁共振距离约束、全原子立体接触、主干phi、psi角、侧链旋转体和其他几何结构的任何较差匹配，以使得能够对单个构象进行校正或定义新的约束以进行进一步的集合精化，从而最大化地符合数据和其他标准。方法学将在改进新的核磁共振结构的过程中进行测试，扩展到其他核磁共振实验数据类型，并尽可能实现自动化。所有结果，包括任何新的方法，都将以网络服务的形式公布，供学生和研究人员使用。

DESCRIPTION (provided by applicant): The long-term goals of this project are to better understand, and to improve upon, the structural characterization and refinement processes for macromolecules by modifying new structure-improvement techniques (developed and proven effective for crystal structures) for application to Nuclear Magnetic Resonance Spectroscopy (NMR) structures. More accurate, detailed structures from either method will help in understanding biological function and aid the drug design and protein design work in numerous medical applications. The approach that will be employed is to use real-time-updatable visualizations that emphasize any poor matches of NMR distance restraints, all-atom steric contacts, backbone phi, psi angles, sidechain rotamers, and other geometry versus the current local model to enable either correction of individual conformations or definition of new restraints for further ensemble refinement, thus maximizing agreement both to data and other criteria. Methodology will be tested during refinement of new NMR structures, extended to other NMR experimental data types, and automated as far as feasible. All results, including any new methodologies, will be published and provided as a web service for use by students and researchers.