The objective of this project is to develop and apply computational methods to design novel proteins. Protein engineering is a potentially powerful method for designing functional proteins such as enzymes, biosensors, and binding proteins, and for improving the properties of natural proteins for industrial applications. As a demonstration of a practical application, natural proteins containing disulfide bonds will be redesigned to remove the disulfide bonds. This may permit the production of these industrially important proteins with inexpensive bacterial expression systems. Computer-assisted protein design is a powerful method for testing our understanding of the underlying physical principles that dictate protein folding and function.
Computer-assisted protein design also has much potential for practical applications. For example, proteins can be engineered to be specific and sensitive sensors for molecules such as toxins. Many chemical syntheses require heating reactants to high temperatures and/or the use of environmentally damaging solvents and catalysts, and often result in significant side-products. Artificial enzymes could reduce the energy and toxic waste used and produced by industrial chemical synthesis, and may also increase the overall yield of desired enantiomerically specific products. There is much excitement and promise for the nascent field of nanotechnology. Proteins are the original nanotechnology. Their ability to adopt specific complex shapes is unmatched by any other class of compound, natural or artificial. Students will learn how to write computer programs, develop optimization algorithms, and model the basic physics of the factors involved in protein folding and binding. They will also learn a variety of experimental techniques such as gene cloning, protein expression and purification, biophysical chemical characterization of protein stabilities and binding affinities, and macromolecular structure determination. The mix of both experimental and theoretical work required for this project will offer a unique educational experience.
