Dr. Colin Smith Receives CAREER Grant from National Science Foundation (NSF)

Colin Smith, Professor of Chemistry

“Dynamics of Computationally Designed Fluorescent Proteins”

The goal of the research is to study and optimize the movement of microscopic, computationally designed proteins that use light to track the locations of biological molecules and reveal how living organisms work. While the structure of a protein is almost always necessary for function, it is often not sufficient. This project focuses on the critical but often neglected role of protein motion in enabling absorbance and reemission of light, a process known as fluorescence. We will first determine which protein shapes either enhance or inhibit fluorescence through detailed analysis of computer simulations and extensive experimental structural characterization. Second, we will test our models through redesign and experimental examination of brighter fluorescent protein variants. As part of these efforts, we will develop a general-purpose computer algorithm that enables rapid evaluation of how thousands of potential mutations affect the shape of the protein. Third, we will investigate the structural determinants of other important properties like the ability of the protein to prevent or facilitate switching fluorescence on and off. The ultimate aim of this project is to develop a detailed understanding of how these fluorescent proteins can be redesigned to make them truly useful tools for biological research. This will enable the creation of even more advanced versions of these and other protein machines (like enzymes) that can also help in the manufacture and recycling of materials at the chemical level.