Predoctoral Fellowships for Students with Disabilities

描述（由申请人提供）：本项目的长期目标是通过修改新的结构改进技术（已开发并证明对晶体结构有效）以应用于核磁共振光谱（NMR）结构，更好地理解和改进大分子的结构表征和精制过程。更准确，更详细的结构，从任何一种方法将有助于了解生物功能，并帮助药物设计和蛋白质设计工作在许多医疗应用。将采用的方法是使用实时可更新的可视化，其强调NMR距离约束、全原子空间接触、主链phi、psi角、侧链旋转异构体和其他几何结构与当前局部模型的任何不良匹配，以使个体构象的校正或新约束的定义能够用于进一步的系综细化，从而最大化与数据和其他标准的一致性。方法将在新的NMR结构的改进过程中进行测试，扩展到其他NMR实验数据类型，并尽可能自动化。所有结果，包括任何新方法，都将作为网络服务发布和提供，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.