Faculty

Understanding the forces that determine the structure of proteins, peptides, nucleic acids, and complexes and assemblies containing these molecules as well as the processes by which the structures are adopted is essential to extend our knowledge of the molecular nature of structure and function. To address such questions, we use statistical mechanics, molecular simulations, statistical modeling, and quantum chemistry.

Creating atomic-level models to simulate biophysical processes (e.g., folding of a protein or binding of a ligand to a biological receptor) requires (1) the development of potential energy functions that accurately represent the atomic interactions and (2) the use of quantum chemistry to aid in parameterizing these models. Calculation of thermodynamic properties requires the development and implementation of new theoretical and computational approaches that connect averages over atomistic descriptions to experimentally measurable thermodynamic and kinetic properties.

Interpreting experimental results at more microscopic levels is fueled by the development and investigation of theoretical models for the processes of interest that range form atomic level detail to more coarse-grained molecular representations. Massive computational resources are needed to realize these objectives, and this need motivates our efforts aimed at the efficient use of new computer architectures, including large supercomputers, Linux Beowulf clusters, and computational grids. Each of the objectives and techniques mentioned represents an ongoing area of development within our research program.

For more information, check out the Brooks Lab website.

Awards

Alfred P. Sloan Foundation Fellow
Fellow of the American Association for the Advancement of Science
North American Editor-in-Chief of the Journal of Computational Chemistry
Computer World/Smithsonian Award in Computational Science

Representative Publications

1. Zhong, L., Matthews, JF., Crowley, MJ., Rignall, T., Talon, C., Cleary, JM., Walker, R.C., Chukkapalli, G., McCabe, C., Nimlos, M.R., Brooks, C.L. III, Himmel, M.E., and Brady, J.W. "Interactions of the Complete Cellobiohydrolast I from Trichodera reesei with Microcrystalline Cellulose", Cellulose, 2008, 15, 261.

2. Szurmant, H., Bu, L., Brooks, C.L. III, & Hoch, J.A. "An essential sensor histidine kinase controlled by transmembrane helix interactions with its auxiliary proteins", Proc. Natl. Acad. Sci., USA 2008, 105 5891.

3. Mannige, R.V. & Brooks, C.L. III. "On the tilable nature of virus capsids and the role of topological constraints in natural capsid design", Phys. Rev., 2008, E 77, 051902.

4. Bu, L & Brooks, C.L. III. "De novo prediction of the structures of M. tuberculosis membrane proteins", J. Am. Chem. Soc., 2008, 130, 5384.

5. Thorpe, I.F. & Brooks, C.L. III. "Molecular evolution of affinity and flexibility in the immune system." Proc. Natl. Acad. Sci. U.S.A, 2007, 104, 8821.

6. Nguyen, H.D., Reddy, V.S. & Brooks, C.L. III. "Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids", Nano. Lett., 2007, 7, 338.

7. Khavrutskii, I.V., Price, D.J., Lee, J. & Brooks, C.L. III. "Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate", Protein Sci., 2007, 16, 1087.