About Me
Denise Okafor received her B.S. in biomedical chemistry from Oral Roberts University. She earned an M.S. in chemistry and a Ph.D. in biochemistry at Georgia Institute of Technology. Her dissertation research was focused on the metallobiochemistry of RNA, investigating RNA folding and function as mediated by divalent cations magnesium and iron. Her postdoctoral research in the Ortlund lab at Emory University was focused on nuclear receptors, a family of ligand-regulated transcription factors. She used molecular dynamics simulations to investigate the mechanisms underlying ligand activation in nuclear receptors. As an NIH-IRACDA postdoctoral fellow, Denise also taught at Morehouse and Spelman colleges in Atlanta.
Program or Departmental Affiliations
BMMB Graduate Program | The Department of Chemistry |
Research Summary
We investigate structural mechanisms of signaling and regulation in protein complexes. We use MD simulations to determine how conformational dynamics of proteins are altered in different functional states. A broad range of biochemical and structural techniques are also employed. Combined, these allow us to carefully elucidate molecular mechanisms that govern the regulation of protein function. By understanding how proteins are regulated endogenously, we aim to identify novel strategies to selectively modulate protein function. Nuclear receptors are one of our favorite classes of molecules to study, because of the fascinatingly complex but elegant allosteric regulatory mechanisms that drive their function. They also play critical roles in metabolism, development, reproduction and other biological processes, which make them highly attractive therapeutic targets.
Honors and Awards
Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biophysics
Cottrell Scholars Award, 2024
Marion Milligan Mason Award, 2023
NIH Director's New Innovator Award, 2022
NSF CAREER Award, 2022
Kavli Fellow, 2020
Keystone Symposia Fellow, 2019-2020
Burroughs Wellcome Fund Career Award at the Scientific Interface, 2018-2023
Ford Foundation Postdoctoral Fellowship, 2018 (declined)
Protein Society Hans Neurath Outstanding promise Travel Award, 2018
NIH-IRACDA Postdoctoral Fellow, 2015-2018
Selected Publications
Yu T; Biswas A; Dube N; Okafor CD*. Simulations reveal unique roles for the FXR Hinge in the FXR-RXR nuclear receptor heterodimer. ACS Bio & Med Chem Au. 2024, 5(1)
Biswas, A; Eisert-Sasse, R.K.; Okafor CD*. Impact of replicas and simulation length on in silico behaviors of a protein domain. ChemPhysChem. 2024, e202400783
Yu T, Villalona P, Khan S.H; Mikeasky, N.; Meinert, E.; Magafas, J.; Pulahinge, T.; Bader, and Okafor, CD* Enhanced Dynamic coupling in a nuclear receptor underlies ligand activity. J. Biol. Chem. 2025, 301(2)
Hazarika S, Yu T, Biswas A, Dube N, Villalona P, Okafor CD* Nuclear receptor interdomain communication is mediated by the hinge with ligand specificity. J. Mol. Biol. 2024 436(22)
Khan, S.H.; Dube, N.; Sudhakar, N.; Fraser, O.; Villalona, P.; Braet, S.M.; Leedom, S.; Reilly, E.R.; Sivak, J.; Crittenden, K.; and Okafor, CD* Ancient and modern mechanisms compete in progesterone receptor activation. RSC Chem. Biol. 2024, 5(518-529)
Hazarika, S.; Fehrle, M. and Okafor, CD* How nuclear receptors transition between active and inactive forms: An energetic perspective. J. Chem. Phys. 2024, 160(11):115102
Mays, S.G.; Hercules, D.; Ortlund, E.A. and Okafor, CD* The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits. Protein Science 2023 32(10):e4754
Dube, N.; Khan, S.H., Sasse, R. and Okafor, C.D*. Identification of an Evolutionarily Conserved Allosteric Network in Steroid Receptors, Journal of Chemical Information and Modeling 2023. https://doi.org/10.1021/acs.jcim.2c01096
Khan, S.H.; Braet, S.M.; Koehler, S.J.; Elacqua, E.; Anand, G.S. and Okafor, C.D*. Ligand-induced shifts in conformational ensembles that describe transcriptional activation eLife 2022, 11:e80140 https://doi.org/10.7554/eLife.80140
Okafor, C.D.; Hercules, D.; Kell, S.A.; and Ortlund E.A. Rewiring ancient residue interaction networks drove the evolution of specificity in steroid receptors. Structure 2020