Allosteric interaction of potential K-Ras inhibitors Drug Design
Ras self-assembely in raft membraneRas Nanoclustering
Ras membrane interaction Protein-Membrane Interactions
Development of Ras inhibitors Drug Discovery
Effects of Ras and cholesterol concentrations on nanocluster propertiesRas Nanoclustering
pMD-membrane: A method for ligand binding site identificationDrug Discovery
Confocal imaging and FCS analysis of Ras in cellsRas Aggregation
Determination of ligand-binding preference to allosteric sitesMethods Development
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Aiming at developing new treatment modalities for unsolved health challenges, our laboratory combines computer simulations with cell biology and biophysical experiments to study the basic principles of bio-molecular function. These include such key cellular phenomena as organization of cell signaling components, interfacial interactions and allostery. Our studies encompass the atomic, molecular and supra-molecular levels of detail, with our primary current focus being the Ras family of lipid-modified enzymes that regulate a variety of cell signaling pathways. We work towards elucidating how dynamics and lateral distribution of Ras and related G-proteins on membrane surfaces regulate signaling events, and leverage insights from our basic research to design novel anti-cancer drugs. Other interests of the group include membrane biophysics, transient signaling complexes, and partitioning of specific drugs into membranes.

Recent Publications

  1. Prakash P, Sayyed-Ahmad A, Cho K-J, Dolino DM, Chen W, Li H, Grant BJ, Hancock JF, Gorfe AA "Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers", 2017, Scientific Reports, 7:40109.
  2. Zhou Y, Prakash P, Liang H, Cho KJ, Gorfe AA and Hancock JF. "Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output", 2016, Cell, 168: 1–13.
  3. Sayyed-Ahmad A, Cho K-J, Hancock JF and Gorfe AA, "Computational Equilibrium Thermodynamic and Kinetic Analysis of K-Ras Dimerization through an Effector Binding Surface Suggest Limited Functional Role" Journal of Physical Chemistry B, 2016, 120(33):8547-8556.
  4. Prakash P, Zhou Y, Liang H, Hancock JF and Gorfe AA, "Oncogenic K-Ras binds to an anionic membrane in two distinct orientations: A molecular dynamics analysis" Biophysical Journal, 2016, 110 (5), 1125–1138.
  5. Lin X, Li Z and Gorfe AA, "Reversible Effects of Peptide Concentration and Lipid Composition on H-Ras Lipid Anchor Clustering" Biophysical Journal, 2015, 109(12):2467-70.
  6. Prakash P, Sayyed-Ahmad A and Gorfe AA, "pMD-membrane: A method for ligand binding site identification in membrane-bound proteins" PLoS Comput Biol 2015, 11(10): e1004469.

Open positions

Occassionaly, positions for postdoctoral fellows in experimental or computational structural biology and biophysics may become available. Interested applicants please contact Dr Gorfe with a detailed CV and statement of research interests. We also accept applications from graduate and undergraduate students for thesis or summer research

Major support