Overview



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

Hualin L and Gorfe AA
Membrane Remodeling by Surface-Bound Protein Aggregates: Insights from Coarse-Grained Molecular Dynamics Simulatione 
The Journal of Physical Chemistry Letters (published online: April 3, 2014) 


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.