EAGER: A novel approach to improve template-based multi-domain protein structure prediction

美国国家科学基金会使用探索性研究的早期概念拨款（EAGER）资助机制来支持在未经测试但具有潜在变革性的研究思路或方法的早期阶段的探索性工作。这个EAGER项目是由于Dear Colleague Letter NSF 16-080邀请来自历史上的黑人学院和大学的申请者提交提案，以加强该机构教师的研究能力而获得的。北卡罗来纳农工州立大学（NC A&amp；T）的项目旨在获得初步数据，以支持尖端研究，设计新的计算工具来模拟多结构域蛋白质结构。结构域的空间排列对于理解多结构域蛋白的功能机制至关重要。该项目还将有助于扩大北卡罗来纳理工学院学生对蛋白质模型研究的参与，使其成为一个不断发展的研究企业。本研究旨在获得初步数据，以设计新的计算工具，以增强基于模板的方法预测多结构域蛋白的能力。从本质上讲，本文将系统地分析当前PDB （Protein Data Bank）中用于建模多结构域蛋白质的全域求解模板结构的可用性。这项系统的研究评估了PDB中多结构域蛋白模板的可用性，将揭示多结构域蛋白模板的可用性程度。这些多结构域的蛋白质通常不适合基于生化实验技术的结构测定，而且这些蛋白质也可以表现出结构域间的灵活性，这可能使结晶复杂化或阻止结晶。因此，多结构域蛋白结构的实验测定往往比单结构域蛋白更难。在系统研究的基础上，还将努力开发一种新的策略来识别远缘或非同源模板结构。这将使用复杂的基于匹配的策略来执行。这一发现的结果将大大提高我们对多结构域蛋白质结构的建模能力，并将有助于增加我们对蛋白质复合物的理解。这个EAGER项目由生物学理事会资助。

The National Science Foundation uses the Early-concept Grants for Exploratory Research (EAGER) funding mechanism to support exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches. This EAGER project was awarded as a result of the invitation in the Dear Colleague Letter NSF 16-080 to proposers from Historically Black Colleges and Universities to submit proposals that would strengthen research capacity of faculty at the institution. The project at North Carolina A&T State University (NC A&T) aims to obtain preliminary data to support cutting-edge research to design novel computational tools to model multi-domain protein structure. The spatial arrangement of domains is essential in understanding the functional mechanisms of a multi-domain protein. This project will also help broaden the participation in protein modeling research of students at NC A&T with a growing research enterprise.This study aims to obtain preliminary data to design novel computational tools to enhance capabilities of template-based approaches for prediction of multi-domain proteins. Essentially, the availability of full-domain solved template structures for modeling multi-domain proteins in current PDB (Protein Data Bank) will be systematically analyzed. This systematic study to assess the availability of templates for multi-domain proteins in PDB will shed light on the extent of availability of templates for multi-domain proteins. These multi-domain proteins are generally not suitable for structure determination based on biochemical experimental techniques, and these proteins can also exhibit inter-domain flexibility, which can complicate or prevent crystallization. As a consequence, experimental determination of the structure of multi-domain proteins is often more difficult than for single domain proteins. Based on the systematic study, efforts will also be made to develop a novel strategy to identify distant or non-homologous template structures. This will be performed using complex matching based strategy. The results of the finding will significantly increase our ability to model multi-domain protein structure and will help to increase our understanding of protein complexes.This EAGER project is funded by the Biology Directorate.