Grant: Discovery Grants Program - Individual

Proteins are one of the fundamental building blocks of the cells in our bodies. They are composed of long chains of 20 amino acids, and the sequence of the amino acids along the protein direct the shape and function of the protein. The same protein in different organisms usually have a dramatically amino acid order and composition, demonstrating that the same protein can be constructed in many different ways. We are seeking to understand how the sequence of amino acids directs the folding and function of the protein by studying the positions that vary among the proteins with the same function in different organisms. We have generated a series of tools that find pairs of positions in the sequence that covary, that is, if one position changes the other position changes. We propose to examine how these covarying positions affect the structure and function of the protein. Understanding how covariant positions arise and contribute to protein structure and function will allow investigators to design better enzymes for industrial (eg. brewing) and home use (eg. cleaning products) and will also allow us to understand diseases that are caused by protein misfolding (eg. mad cow disease, Alzheimers)