Dr. Alemayehu A. Gorfe
The University of Texas Health Science Center at Houston
Department of Integrative Biology and Pharmacology
- Computer Simulation of Cell Signaling and Molecular Transport
- Structure-based Drug Design
- Signaling Complexes
- Membrane-protein Interaction
- Structure and Dynamics of Interfaces
- Allostery in Supramolecular Assemblies
A major interest of our lab is to understand the thermodynamic principles of specificity in cell signaling and molecular transport by means of computational and theoretical techniques. The advent of petaflop computational resources and the fast-paced progress in coarse-grained modeling create unprecedented opportunities for simulating processes that span a vast range of time and length scales, such as cell signaling and molecular transport. These computational studies will allow us to investigate normal and aberrant properties of protein-protein and protein-membrane complexes in atomic detail. Other areas of interest include the basis of allosteric communication in signaling complexes, enzyme catalysis, molecular recognition and drug design. We develop and apply a variety of computational techniques, including classical and advanced molecular and Brownian dynamics simulations, structural bioinformatics, binding free energy calculations and related methods. Results from these studies will be the engines of new concepts and hypotheses to drive discovery efforts and experimental work.
Current projects include the spatiotemporal membrane organization of Ras proteins and their reaction partners, the driving forces for the membrane translocation of positively charged proteins and peptides, identification of novel allosteric sites in proteins and characterization of the communication between those sites. These projects are carried out in close collaboration with experimental labs.
A tutorial in my laboratory would provide experience with modern techniques in biomolecular simulations, including molecular dynamics and Brownian dynamics simulations; structure based drug design; structural bioinformatics; continuum electrostatics and theoretical approaches for investigating the thermodynamic principles underlying the assembly and function of supramolecular complexes.
P Prakash, A Sayyed-Ahmad, AA Gorfe. The role of conserved waters in the conformational transitions of Q61H Kras. PLoS Comput Biol, 8: e1002394, 2012.
L Janosi, Z Li, FJ Hancock and AA Gorfe. Organization, Dynamics and Segregation of Ras Nanoclusters in Membrane Domains. PNAS, 109: 8097-102, 2012.
AA Gorfe and HJ Hocker. Membrane Targeting: Methods. In eLS. John Wiley & Sons, Ltd: Chichester (2012).
J Durrant, R Cao, AA Gorfe, W Zhu, J Li, E Oldfield, JA McCammon. Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design. Chem. Biol. Drug Des., 78:323-332, 2011.
BJ Grant, S Lukman, H Hocker, J Sayyah, J Heller Brown, JA McCammon, AA Gorfe. Novel Allosteric Sites on Ras for Lead Generation. PLoS ONE, 6:e25711, 2011.
AA Gorfe. Mechanisms of Allostery and Membrane Attachment in Ras GTPases: Implications for Anti-cancer Drug Discovery. Curr Med Chem, 17: 1-9, 2010.
BJ Grant, AA Gorfe and JA McCammon. Large Conformational Changes in Proteins: Signaling and Other Functions. Curr Opin, Struct Biol, 20:142-147, 2010.
D Abankwa, AA Gorfe, K Inder and JF Hancock. Membrane orientation and nanodomain organization generate Ras isoform diversity. PNAS, 107:1130-1135, 2010.
A Sayyed-Ahmad, LM Lichtenberger and AA Gorfe. Structure and dynamics of cholic acid and dodecylphosphocholine-cholic acid aggregate. Langmuir, 26: 13407-13414, 2010.
S Lukman, B Grant, AA Gorfe, G Grant and JA McCammon. Distinct dynamics of K-ras and H-ras A59G. PLoS Comput Biol, 6:e1000922, 2010.
L Janosi and AA Gorfe. Simulating POPC and POPC/POPG Bilayers: Conserved packing and altered surface reactivity. J Chem Theory Comput, 16:3267-3273, 2010.
L Janosi and AA Gorfe. Importance of the sphingosine base double bond geometry for the structural and thermodynamic properties of sphingomyelin bilayers. Biophys J, 99:2957-2966, 2010. (FEATURE ARTICLE)
B Grant, JA McCammon and AA Gorfe. Conformational selection in G-proteins: lessons from Ras and Rho. Biophys J 99: L87-L89, 2010 (FEATURE ARTICLE)
L Janosi and AA Gorfe. Segregation of negatively charged phospholipids by the polycationic and farnesylated membrane anchor of Kras. Biophys J, 99: 3666-3674, 2010.
Y Zhou, B-Z Lu and AA Gorfe. Continuum Electromechanical Modeling of Protein Membrane Interactions. Phys Rev E, 82: 41923-41928, 2010.
Program in Biochemistry and Molecular Biology