Research:
Cellular processes and life are ultimately regulated by the actions of biomolecules. Molecular biophysics techniques allow the quantitative examination of atomic and molecular motions in specific biomolecules and their interactions in macromolecular complexes. Our particular research interests are focused on investigating how protein folding and assembly impacts important signaling processes and on understanding the basic biophysical rules that govern those processes. Towards this goal we have developed combined experimental/theoretical tools to investigate the energy landscape that controls the folding/misfolding of proteins. Proteins, however, do not have one landscape for folding and another for function. The real challenge we are undertaking is to generalize these ideas to accommodate both folding and function. Ultimately, we are working towards understanding the molecular basis for specific signaling molecule binding and organelle/cellular response. For this reason, we test ideas generated from our continued investigations of the folding and function of cytokine Interleukin-1b (IL-1b) on diverse structural systems such as protein kinases, green fluorescent protein and the mitoNEET family of proteins. We are continuing to develop methodologies to investigate how folding is linked to function and are applying and further developing approaches to investigate how the native energy landscape of signaling enzymes control recognition, allosteric modulation, substrate binding and activity in vitro, in vivo and in silico.
Folding and Functional Interplay in IL-1B
Characterization of the Conformational Ensemble in the C-Terminal Src Tyrosine Kinases.