We combine simulation and experiment to understand protein conformational changes, their role in signaling, and opportunities they present for drug design. For example, the movie shows the opening of an unexpected binding pocket that we have demonstrated may be a valuable drug target for combating antibiotic resistance. We are also interested in understanding the roles such conformational changes play in signaling cascades, such as those responsible for vision.
Sukrit Singh and Gregory R. Bowman
Quantifying allosteric communication via both concerted structural changes and conformational disorder with CARDS
J. Chem. Theory Comput. (2017) (Abstract)
Shen G., Cui W., Zhang H., Zhou F., Huang W., Liu Q., Yang Y., Li S., Bowman G.R., Sadler J.E., Gross M.L., and Li W.
Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer.
Nature Structural & Molecular Biology 24, 69–76 (2017). (Abstract)
Featured in News and Views, Nature Structural & Molecular Biology 24, 5–6 (2017).
Chris A. Brosey, Chris Ho, Winnie Z. Long, Sukrit Singh, Kathryn Burnett, Greg L. Hura, Jay C. Nix, Gregory R. Bowman, Tom Ellenberger, and John A. Tainer
Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor
Structure (2016) (Abstract)
Pascolutti, R., Sun, X., Kao, J., Maute, R., Ring, A.M., Bowman, G.R. and Kruse, A.C.
Structure and Dynamics of PD-L1 and an Ultra High-Affinity PD-1 Receptor Mutant.
Structure (e-pub ahead of print) (2016)
Accurately modeling nanosecond protein dynamics requires at least microseconds of simulation.
J Comput Chem. 37(6):558-66. (2016) (Abstract)
DuBay, K.H., Bowman, G.R. and Geissler, P.L.
Fluctuations within Folded Proteins: Implications for Thermodynamic and Allosteric Regulation
Acc. Chem. Res. 48:1098-1105 (2015). (Abstract)
Bowman, G.R. Bolin, E.R., Hart, K.M., Maguire, B.C. and Marqusee, S.
Discovery of multiple hidden allosteric sites by combining Markov state models and experiments
PNAS 112:2734-2739 (2015). (Abstract)