Chemistry Associate Professor Dennis Livesay Receives $960,000 Research Grant

Chemistry Associate Professor Dennis Livesay  Receives $960,000 Research Grant
Chemistry associate professor Dennis Livesay has been awarded a $960,000 research grant for work on ?Predicting Protein Flexibility and Stability.?

Chemistry associate professor Dennis Livesay has been chosen to receive a $960,000 research grant for work on “Predicting Protein Flexibility and Stability” from the National Institutes of Health. Livesay will share the grant with collaborator Donald Jacobs of the University of North Carolina, Charlotte.

“Livesay received one of  the most competitive of the grants the NIH offers,” says Donald Straney, dean of the College of Science. “It represents a singular confirmation of the quality of Dennis's work. We are fortunate to have a researcher of his caliber on campus working with our students. His accomplishments reflect well on the Chemistry department's ability to mentor students and junior faculty.”

Livesay specializes in computational biology and bioinformatics, the use of techniques from applied physics, mathematics, informatics, statistics and computer science to solve biological problems. He and Jacobs are exploring the balance between protein flexibility and protein stability. This balance is critical for proteins to function properly. For example, a protein requires flexibility to perform a given task efficiently, but if the protein is too flexible then it may unfold (denature) and fail to function. Improper protein folding is linked to a variety of medical conditions, including: cystic fibrosis, Alzheimers and even Mad Cow disease.

“This grant will allow us to build a theoretical framework for deciphering these complex physical relationships that are so critical to protein function and disease,” says Livesay.

The grant will support Livesay's and Jacobs's work on developing the next generation of the Distance Constraint Model (DCM), a unique biophysical modeling scheme that simultaneously calculates stability and flexibility metrics. The DCM represents a promising approach to understand how evolution balances protein stability and protein flexibility, whereas most traditional methods (computational and experimental) can only probe one or the other. Livesay's and Jacobs's project builds upon prior success of using graph-rigidity algorithms to identify flexible and rigid regions in proteins, and development of the Distance Constraint Model (DCM).

Livesay explains, “There is only one other method that can directly evaluate the give-and-take between stability and flexibility, called molecular dynamics (MD) simulations. However, MD is far too computationally expensive, even with the worlds fastest supercomputers, to be done on a grand scale. The DCM is extremely computationally efficient, and thus provides a means to quantify stability/flexibility relationships within thousands of proteins. Through a better understanding of these relationships, this work will drastically expand our basic understanding of properly functioning proteins, provide molecular-level insight into disease-causing mutations and should provide a direct path to improved computer-aided drug design.”

The NIH grant provides $960,000 over four years, of which approximately $440,000 will come to Cal Poly Pomona. The money will be primarily used to purchase equipment and pay salaries for two post-doctoral researchers and one Ph.D. student. It will also fund development of a quantitative database that will allow researchers across the globe to utilize the data gathered from this project.

A resident of Pomona, Livesay joined Cal Poly Pomona in 1996. Livesay also helped to develop the university's Center for Macromolecular Modeling and Material Design (CM3D). CM3D centralizes a pair of interdisciplinary labs that bring chemists, physicists, engineers and computer scientists all into one research center. By networking 44 personal computers, the professors created a networked computer cluster powerful enough to run millions of DCM calculations. The computer component of CM3D has helped research efforts by students and faculty, including Livesay's protein simulations. Later, the CM3D professors hope to create an experimental lab near the computer lab to centralize specialized equipment from different disciplines in the laboratory.