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 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 at 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.

Open positions

9/26/19: (1) A funded Postdoctoral position may become available to work on molecular simulations and biophysical assays. Qualified candidates may contact Dr Gorfe with a detailed CV and a statement of research interest. (2) We have an immediate opening for a Research Assistant I or Research Assistant II position to assist in cell culture and biophysical assays. Candidates may email their CV to Dr Gorfe. (3) We always accept applications from graduate and undergraduate students for thesis or summer research

Recent Publications

  1. Prakash P and Gorfe AA "Probing the conformational and energy landscapes of KRAS membrane orientation", 2019, Journal of Physical Chemistry B, 2019, 17;123(41):8644-8652.
  2. Gorfe AA, Cho KJ "Approaches to inhibiting oncogenic K-Ras", 2019, Small GTPases, Aug 22:1-10.
  3. Mccarthy M, Pagba CV, Prakash P, Naji AK, van der Hoeveni D, Liang H, Gupta AK, Zhou Y, Cho K-J, Hancock JF, Gorfe AA "Discovery of high affinity non-covalent allosteric KRAS inhibitors that disrupt effector binding", 2019, ACS Omega, 4 (2), 2921–2930.
  4. Prakash P, Litwin D, Liang H, Sarkar-Banerjee S, Dolino D, Zhou Y, Hancock JF, Jayaraman V, Gorfe AA, "Dynamics of Membrane-Bound G12V-KRAS From Simulations and Single-Molecule FRET in Native Nanodiscs", 2019, Biophys J 116(2):179-183.
  5. 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.

Major support