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 pathways and whose malfunction leads to many forms of cancer and developmental disorders. The need for novel therapeautic agents that stop signaling through defective Ras is urgent. We contribute to the search for such agents by studying Ras at the atomic, molecular and supramolecular levels of detail using multi-scale molecular 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 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 (see Research Interests).

Selected Publications

Prakash P, Hancock JF and Gorfe AA
Binding hotspots on K-Ras: Consensus ligand binding sites and other reactive regions from probe-based molecular dynamics analysis 
Proteins 2015, 83(5): 898-909 

Li H and Gorfe AA
Membrane Remodeling by Surface-Bound Protein Aggregates: Insights from Coarse-Grained Molecular Dynamics Simulatione 
The Journal of Physical Chemistry Letters, 2014, 5(8): 1457-1462 

Hocker HJ, Maharaj N and Gorfe AA
LIBSA - Method for the determination of ligand-binding preference to allosteric sites on receptor ensembles 
Journal of Chemical Information and Modeling, 2014, 24;54(2):530-538. 

Prakash P and Gorfe AA
Lessons from computer simulations of Ras proteins in solution and in membrane 
BBA-General Subjects, 2013, 1830(110): 5211-5218 

Hocker JH, Kwang-Jin C, Chung-Ying KC, Rambahal N, Sagineedu SR, Shaari K, Stanslas J, Hancock JF, Gorfe AA
Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function 
Proceedings of the National Academy of Sciences USA, 2013, 110(25):10201-10206. 

Li Z, Janosi L and Gorfe AA
Formation and domain-partitioning of H-ras peptide nanoclusters: Effects of peptide concentration and lipid composition 
Journal of the American Chemical Society, 2012, 134(41):17278-85. 

Prakash P, Sayyed-Ahmad A, Zhou Y, Volk DE, Gorenstein DG, Dial EJ, Lichtenberger LM and Gorfe AA
Aggregation Behavior of Ibuprofen, Cholic Acid and Dodecylphosphocholine Micelles 
BBA-Biomembranes, 2012, 1818(12): 340-347. 

Janosi L, Li Z, Hancock JF and Gorfe AA
Organization, Dynamics and Segregation of Ras Nanoclusters in Membrane Domains 
Proceedings of the National Academy of Sciences USA, 2012, 109(21): 8097-102. 

Prakash P, Sayyed-Ahmad A and Gorfe AA
The Role of Conserved Waters in Conformational Transitions of Q61H K-ras 
PLoS Computational Biology, 2012, 8(2), e1002394.

Complete List: Publications or Google Scholar
Weekly Meeting:
  • Monday (10:30am): Mike
  • Tuesday (10:30am): Amit
  • Tuesday (2:00pm): John
  • Wednesday (9:30am): Xubo
  • Thursday (9:30am): Pri
  • Thursday (2:00pm): Kalkidan
  • Friday (9:30am): Suparna

    Progress Reports
  • Due the first Friday of every even month.

    Journal Watch:
  • Mike/Suparna: MC, EMBO J, Structure, Cell, Biochemistry, JBC
  • Pri: BJ, Bioinformatics, J Mem Biol, Proteins, Protein Science, Journal of General Physiology
  • Amit/Abdallah: PRL, PRE, JCP, J Comput Chem, ChemPhysChem
  • Xubo: JACS, JCTC, JPC, Langmuir, PNAS
  • Alex: Nature series, Science and Review/Opinion Journals

    Group Meeting (Tuesday, 9:30AM, Rm 4.136)
    6/30/2015 Xubo Data / J club
    7/7/2015 Pri Data / J club
    7/14/2015 John Data
    7/21/2015 No Group Meeting
    7/28/2015 No Group Meeting
    8/4/2015 Mike Data
    8/11/2015 Abdallah Data / J club
    8/18/2015 Amit Data
    8/25/2015 Suparna Data