CAREER: A Database for Modeling Protein Spatial Geometry -Discovering Protein Functions

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

Many genes in bacteria, plants, fungi, worm, fruit fly, and human have no sequence matches, their three-dimensional structures are unsolved, and their functional roles are unknown. Three-dimensional spatial surface motifs of key residues can provide critical links connecting gene sequence, protein structure, and protein functions. Surface motifs with complicated geometry are difficult to compute, and the key residues are often from distant parts of the primary sequences. The proposed project aims to develop tools using computational geometry for discovery of similar protein surface patterns, as well as server databases of libraries of similar protein surfaces for biological querying and understanding. The search tools will be developed using a comprehensive informatics approach for discovery of statistically significant similarity relationship of protein surfaces, combining sequence, physicochemical, and shape information. The database of libraries of spatial surface motifs will provide organized information enriched with functional annotation. By providing quantitative, organized, and understandable information of protein surface motifs, the tools and database proposed will help to uncover new patterns of key residues in surface motifs important for understanding protein functions. It will facilitate the understanding of the cellular roles of newly sequenced genes from genomic sequencing and newly solved structures from structural genomics. It will also help to establish previously unrecognized functional and evolutionary relationship of protein spatial surfaces, and uncover deep evolutionary origins of functionally constrained structural elements before the emergence of protein domains and folds. Knowledge and insight gained from protein surface motifs will also help to design and engineer novel proteins for new biological functions and for novel industrial applications. The educational component of this proposal will be centered on (1) course and curriculum development, (2) student mentoring, and (3) outreach. In addition to curriculum development for the newly approved MS/PHD programs in bioinformatics, a new course named "Geometric Computing for Bioinformatics" will be developed, which will be tightly linked to the research through classroom teaching and class projects designed based on the research activities. The involvement of graduate and undergraduate students, as well as postdoctoral researchers provide mentoring opportunities, with the goal to pass the knowledge, the computational skill, and the ability of critical and creative thinking to the students. It will also allow the students to present their research in national and international conferences. The outreach activities to Chicago high school and junior colleges will be focused on high school summer camp activities of bioinformatics research, local visits, hosting interns in the PI's lab, school teacher preparation, and developing career as well as educational material on bioinformatics (CD-ROM and website) to attract students not traditionally represented in this field.