Charles L. Brooks III

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Charlie Brooks Photo

Director of Biophysics; Warner-Lambert/Parke-Davis Professor of Chemistry and Professor of Biophysics

Office Location(s): 4028c Chemistry
Phone: 734.764.1146
Fax: 734.764.3323
Brooks Research Group

  • About

    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.

    Research Image

    Figure Caption

    Using novel methods to incorporate pH directly into molecular simulation studies, Brooks’ group has explored the role pH plays in the formation of amyloid fibrils in peptides from Alzheimer’s Ab peptide. Their findings demonstrate that in low and high pH environments an increased propensity for the peptide to adopt helical conformations acts to “protect” the peptide from forming oligomers, as precursors to amyloid formation. However, at intermediate values of pH, such as those found in early endosomes, pH ~ 6, conformations revealing the

    maximal exposure of the central hydrophobic core of the Ab peptide supports the formation of oligomers that could ultimately lead to amyloid fibrils or larger oligomeric states that may be involved in the Alzheimer pathology. The structures shown represent the centroids of the most populated conformational clusters observed in molecular dynamics simulations carried out at the indicated pH values. At pH=6 the central hydrophobic core is displayed in a van der Waals representation. The putative dimer structure is meant to be suggestive of formation of early oligomers and is a hypothetical structure for purposes of illustration. The figure was adapted from Khandogin & Brooks, Proc Natl Acad Sci, USA, 104: 16880 (2007).


  • Education
    • Ph.D., Purdue University
    • PostDoc, Harvard University
  • Awards
    • Hans Neurath Award-Protein Society, 2012
    • Alfred P. Sloan Foundation Fellow
    • Fellow of the Biophysical Society
    • Fellow of the Royal Society of Chemistry
    • 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
  • Research Areas of Interest
    • Theoretical and Computational Biophysics and Chemistry/Biophysical Chemistry/Physical Chemistry
  • Selected Publications:
  • Articles