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.
Hart K.M., Moeder K.E., Ho C.M.W., Zimmerman M.I., Frederick T.E., and Bowman G.R.
Designing small molecules to target cryptic pockets yields both positive and negative allosteric modulators.
PLoS One. 12(6):e0178678. doi: 10.1371/journal.pone.0178678. eCollection. (2017) (Abstract)
Sun X., Laroche G., Wang X., Ågren H., Bowman G.R., Giguère P.M., and Tu Y.
Propagation of the Allosteric Modulation Induced by Sodium in the δ-Opioid Receptor.
Chemistry 23(19):4615-4624 (2017) (Abstract)
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)
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. 24(12):2067-2079. (2016) (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.
Nat Struct Mol Biol. 24(1):69-76. (2017). (Abstract)
Featured in News and Views, Nature Structural & Molecular Biology 24, 5–6. (2017)
Accurately modeling nanosecond protein dynamics requires at least microseconds of simulation.
J Comput Chem. 37(6):558-66. (2016) (Abstract)