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

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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.