Education & Training
- Postdoctoral Fellow
- University of California, San Diego, 2008
- Postdoctoral Fellow
- University of Zurich, Switzerland, 2005
- University of Zurich, Switzerland, 2003
We use computer simulations to study the organization of cell signaling components, interfacial interactions and allostery to aid in the development of treatments for unsolved health challenges. Our special focus is on the Ras family of lipid-modified enzymes that regulate a variety of cell signaling pathway and whose malfunction leads to many forms of cancer. There is an urgent need for an ongoing effort to find drugs that abrogate signaling through defective Ras. Aiming at contributing to this effort, we study Ras at the atomic, molecular and supramolecular levels of detail using multi-scale simulations and collaborative cell-biological and biophysical experiments. We are particularly interested in understanding how dynamics and lateral distribution of Ras and related G-proteins on membrane surfaces may affect their ability to functionally interact with other proteins. Other interests of the group include modeling transient signaling complexes and interaction between specific drugs and phospholipids.
A tutorial in our laboratory would provide experience with modern techniques in biomolecular simulations for investigating the thermodynamic principles underlying the assembly and function of molecular complexes.
- Zhenlong Li and Gorfe AA. (2014). Modulation of a Small Two-Domain Lipid Vesicle by Linactants. J Physical Chemistry B, 18(30): 9028-9036.
- Hualin Li and Gorfe AA. (2014). Membrane Remodeling by Surface-Bound Protein Aggregates: Insights from Coarse-Grained Molecular Dynamics Simulation. J Physical Chemistry Lttrs, 5(8): 1457-1462.
- Prakash P and Gorfe AA. (2014). Overview of simulation studies on the enzymatic activity and conformational dynamics of the GTPase Ras. Molecular Simulation, 40(10-11): 839-847.
- Hocker HJ, Maharaj N and Gorfe AA. (2014). LIBSA – Method for the determination of ligand-binding preference to allosteric sites on receptor ensembles. J Chemical Info and Modeling, 24;54(2):530-538.
- Ramaswamy SS, MacLean DM, GorfeAA, Jayaraman V. (2013). pH induced conformational changes in Acid Sensing Ion Channel. J Biol Chem., 288, 35896-35903.
- Prakash P, Gorfe AA. (2013). Lessons from computer simulations of Ras proteins in solution and in membrane. BBA-Gen Subj., 1830, 5211-5218.
- Li Z, Gorfe AA. (2013). Deformation of a two-domain lipid bilayer due to asymmetric insertion of lipid-modified Ras peptides. Soft Matter., 9,11249-11256.
- Prakash P, Gorfe AA. (2013). Phosphatidylcholine attenuates aggregation of non-steroidal anti-inflammatory drugs with bile salts. Biochemistry. 52, 7461–7469.
- Brand CS, Hocker HJ, Gorfe AA, Cavasotto CN, Dessauer CW. (2013). Isoform Selectivity of Adenylyl Cyclase Inhibitors: Characterization of Known and Novel Compounds. J Pharm Exp Therap., 347, 265-275.
- Li H, Gorfe AA. (2013). Aggregation of full-length H-Ras protein in bilayer: Simulations with the Martini force field. PLoS ONE. 8, e71018.
- Hocker HJ, Cho K-J, Chen C-YK, Rambahal N, Sagineedu SR, Shaari K, Stanslas J, Hancock JF, Gorfe AA. (2013). Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function. Proc Natl Acad Sci U S A., 110, 10201-10206.
- Cho KJ, Park JH, Piggott AM, Salim AA, Gorfe A, Parton RG, Capon RJ, Lacey E, Hancock JF. (2012). Staurosporines disrupt phospha- tidylserine trafficking and mislocalize Ras proteins. J Biol Chem., 287, 43573-43584.
- Janosi L, Li Z, Hancock JF and Gorfe AA. (2012). Organization, dynamics and segregation of Ras nanoclusters in membrane domains. Proc Natl Acad Sci. 109, 8097-8102.
- Li Z and Gorfe AA. (2012). What drives the clustering of membrane-bound Ras? Small GTPases., 3, 244-247.
- Li Z, Janosi L and Gorfe AA. (2012). Formation and domain-partitioning of H-ras peptide nanoclusters: Effects of peptide concentration and lipid composition. J Am Chem Soc., 134, 17278-1728.
- Prakash P, Sayyed-Ahmad A, and Gorfe AA. (2012). The role of conserved waters in conformational transitions of Q61H K-ras. PLoS Comput Biol., 8, e1002394.
- Prakash P, Sayyed-Ahmad A, Zhou Y, Volk DE, Gorenstein DG, Dial EJ, Lichtenberger LM, Gorfe AA. (2012). Aggregation behavior of ibuprofen, cholic acid and didecylphosphatidylcholine micelles. Biochim Biophysica Acta., 1818: 3040-3047.
- Grant BJ, Lukman S, Hocker H, Sayyah J, Heller Brown J, McCammon JA, Gorfe AA. (2011). Novel Allosteric Sites on Ras for Lead Generation. PLoS ONE, 6, e25711.
- Janosi L, and Gorfe AA. (2010). Simulating POPC and POPC/POPG Bilayers: Conserved packing and altered surface reactivity. J Chem Theory Comput., 16, 3267-3273.
- Janosi L, and Gorfe AA. (2010). Importance of the sphingosine base double bond geometry for the structural and thermodynamic properties of sphingomyelin bilayers. Biophys J., 99, 2957–2966. (FEATURED ARTICLE)
- Janosi L, and Gorfe AA. (2010). Segregation of negatively charged phospholipids by the polycationic and farnesylated membrane anchor of Kras. Biophys J., 99, 3666-3674.
- Zhou Lu B-Z, and Gorfe AA. (2010). Continuum Electromechanical Modeling of Protein Membrane Interactions. Phys Rev E., 82, 41923-41928.
- Sayyed-Ahmad A, Lichtenberger LM, and Gorfe AA. (2010). Structure and Dynamics of Cholic Acid and Dodecylphosphocholine−Cholic Acid Aggregates. Langmuir, 26, 13407-13414.
- Abankwa D, Gorfe AA, Inder K and Hancock JF. (2010). Ras membrane orientation and nanodomain localization generate isoform diversity. Proc Nat’l Ac Sc USA., 107:1130-1135.
- Gorfe AA. (2010). Mechanisms of allostery and membrane attachment in Ras GTPases: implications for anti-cancer drug discovery. Curr Med Chem., 17:1-9.
- Grant B, Gorfe AA, and McCammon JA. (2010). Large conformational changes in proteins: signaling and other functions. Curr Opin Struct Biol., 20:142-147.