Craig John Benham
Ph.D., 1972, Princeton University
Refereed publications: Via Math Reviews
Office: MSB 2144
Professor Craig Benham studies the relationship between structure and function in macromolecules such as DNA and proteins. He has an unusually strong interdisciplinary perspective, and has joint appointments at the Departments of Mathematics, Bioengineering, and the Center for Bioinformatics.
For example, he has developed statistical mechanical methods for the analysis of superhelical DNA duplex destabilization. The predictions of this analysis are in precise agreement with experimental results regarding the location and extent of strand separation in DNA sequences. This quantitative accuracy allows these methods to be applied to other sequences, on which experiments have not yet been performed.
He has also investigated the topological properties of protein structures and their functional and evolutionary correlates. The topological properties of greatest interest are the patterns of loops created by disulphide bonds or beta sheet associations, and the knot types of the protein backbone. Benham has enumerated the number of possible topologies that can arise, studied which of these posiblities are realized in known protein structures, and examined the functional and evolutionary relationships between proteins with identical or similar topologies.
Professor Benham has an AB degree in mathematics from Swarthmore College and a Ph.D. in mathematics from Princeton University, where he worked in complex manifold theory. As an assistant professor at the University of Notre Dame he encountered Dr. John Kozak, a theoretical chemist working on protein structure problems. He became interested in the field because many of the important problems had significant mathematical components. "To get additional training in the area of molecular structure," he recalls, "I spent a year as a postdoc with Dr. Max Delbruck in the Biology Division at the California Institute of Technology. There I switched my interests to DNA, primarily because the mathematical problems relating to DNA structure involved an intricate interplay among topology, geometry, and mechanics. I have been working in this field ever since."
Selected publications Benham, C.J. Sites of predicted stress-induced DNA duplex destabilization occur preferentially at regulatory loci. Proc. Natal. Acad. Sci. USA. 90:2999-3003, 1993.
 Bauer, W.R., and Benham, C.J. The free energy, enthalpy and entropy of native and of partially denatured closed circular DNA. J. Mol. Biol. 234:1184-1196, 1993.
 Benham, C.J., and Jafri, M.S. Disulfide bonding patterns and protein topologies. Protein Science 2:41-54, 1993.
 Bauer, W.R., Ohtsubo, H., Ohtsubo, E. and Benham, C.J. Energetics of coupled twist and writhe changes in closed circular pSM1 DNA. J. Mol. Biol. 253: 438-452, 1995.
 Sun, H.-Z., Mezei, M., Fye, R. and Benham, C.J. Monte Carlo analysis of conformational transitions in superhelical DNA. J. Chem. Phys. 103:8653-8665, 1995.
 Benham, C.J. Duplex destabilization in superhelical DNA is predicted to occur at specific transcriptional regulatory regions. J. Mol. Biol. 255: 425-434, 1996.