Ph.D.: Ben-Gurion University, Israel
Post-doctorate: The National Institutes of Health, USA
Position: Lecturer
Department of Clinical Biochemistry
Faculty of Health Sciences
E-mail: engels@bgu.ac.il
Interaction between bio-molecules as target for pharmacological intervention
Protein-protein interactions (PPI) play an essential role in virtually all cellular processes. In biological systems, information is conveyed by the action of small-molecule messengers (Ca2+, cAMP, neurotransmitters, etc.) and via PPI. While mimetics of the former are widely used to intervene in the functions of biological systems, we have only a rudimentary capacity to manipulate PPI. Increasingly, PPI are appreciated as potential targets for the development of selective tools to modulate the functions of biological systems. PPI targeting using drugs may represent a new strategy to combat diseases that have remained intractable through conventional therapies.
1. Functional mimetics of the extra- and intracellular domains of G protein coupled receptors (GPCR) as a tool for studying the structural basis of GPCR interaction with molecular targets and drug discovery.
2. Combinatorial in vitro selection methods to identifying active compounds targeting protein-protein interactions, in particular formation of GPCR/G protein complexes.
3. Molecular modeling in structure-based drug discovery.
Tikhonova I.G., Sum C.S., Neumann S., Engel S., Raaka B.M., Costanzi S. and Gershengorn M.C. (2008). Discovery of novel agonists and antagonists of the free fatty acid receptor (FFAR1) using virtual screening. Journal of Medicinal Chemistry 51(3): 625–633.
Engel S., Skoumbourdis A., Childress J., Neumann S., Deschamps J.R., Thomas C.J., Colson A.O., Stefano C. and Gershengorn M.C. (2008). A Virtual Screen for Diverse Ligands: Discovery of Selective G Protein-Coupled Receptor Antagonists. Journal of the American Chemical Society 130(15):5115-5123.
Tikhonova I.G., Best R.B., Engel S., Hummer G., Gershengorn M.C. and Costanzi S. (2008). Atomistic insights into rhodopsin activation from a dynamic model. Journal of the American Chemical Society 130(31):10141-10149.
Mendelson M., Yossef R., Appel M.Y., Zilka A., Hadad U., Afergan F., Rosental B., Engel S., Braiman A., and Porgador A. (2012). Dimerization of NKp46 receptor is essential for NKp46-mediated lysis: characterization of the dimerization site by epitope mapping. Journal of Immunology 188(12):6165-6174.
Kuttner Y.Y. and Engel S. (2012). Protein hot spots - the islands of stability. Journal of Molecular Biology 415(2):419-428.
Kuttner Y.Y., Nagar T. and Engel S. (2013). Surface dynamics in allosteric regulation of protein-protein interactions: Modulation of calmodulin functions by Ca2+. PLOS Computational Biology 9(4): e1003028.
