CAREER: An Integrated Approach to Predictive Protein-Protein Docking

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Genomic and proteomic projects have produced a vast amount of biological data: fully sequenced genomes, gene and protein sequences, protein structures, protein-protein interactions, and gene expression patterns. The next grand challenge in Bioinformatics is to determine the biological functions and cellular roles of all genes and proteins, and their interactions with one another to form a functional cell. The research problem aims to computationally predict the 3-dimensional structure of a protein complex from its components. This project will provide insights into the functions of the interacting proteins and can guide the design of novel reagents to regulate protein interaction networks. The research efforts will be integrated with Bioinformatics education. Boston University is among the first to establish a graduate degree program in Bioinformatics, funded by an NSF IGERT grant and growing rapidly. The curriculum development of the Program is a key element of this proposal.This project seeks to build a general system for predictive protein docking: to start with the coordinates of the unbound component proteins and to obtain computationally a model for the complex structure, including the conformational changes upon association. The research team has developed an initial-stage docking algorithm, which compares competitively with the best algorithms with a similar goal. The proposed work includes the following components: (1) To improve the existing docking algorithm, with the goal of initial screening. (2) To develop a new algorithm to refine the structures produced by the initial-stage algorithm. (3) To develop novel target functions for docking algorithms. (4) To test algorithms extensively using a benchmark set and community wide blind tests. (5) To establish a web accessible, fully automated, and user-friendly docking server. Results and the protein complex database produced in this project will also be available at the server. The results of this project will be integrated into two graduate courses (Computational Genomics and Protein Engineering for Biomedical Applications) and one Bioinformatics Teacher's workshop. The courses and workshop will also include other state-of-the-art results in the fields of structural and functional Proteomics and Bioinformatics.