Samy Meroueh
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Assistant Professor
Chemical Biology
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| Ph.D., 2001, Wayne State University, Detroit, MI
Post Doctoral, 2003, Wayne State University, Detroit, MI
Post Doctoral, 2006, University of Notre Dame, Notre Dame, IN
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| Phone: (317)274-8315 |
| Email: smeroueh@iupui.edu |
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Dr. Meroueh's Web Site |
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Research |
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Publications |
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Research
Research in my laboratory is concerned with the design of small molecules and proteins for the purpose of altering cellular processes and developing new anti-cancer therapeutics. We are particularly interested in modulating signaling mediated by cell surface receptors that play critical role in tumor invasion and metastasis. Our molecular designs are performed using structure-based computational biology and chemistry tools and fall into three projects. In the first project we are designing small molecules to bind at the protein-protein interface or at other sites that have the potential for allosteric effects. The second project involves the grafting of stably folded small scaffold proteins to bind to unrelated receptors and to modulate their interactions and signaling. The third project follows a systems biology approach whereby structural information from the human proteome is used to guide our efforts. We follow a chemical biology route where we validate our designs and characterize the mechanism of action of designer molecules using various biochemical, biophysical, structural and cell culture-based techniques.
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Li, L.; Bumerdene, K.; Baenziger, P. H.; Hemmert, J. R.; Rosen, J.; Nellis, J.; Pierce, M. ; Meroueh, S. O.
2009 BioDrugScreen: A Computational Drug Design Resource for Ranking Molecules Docked to the
Human Proteome, Nucleic Acid Research, in press.
Xue, B., Oldfield, C., Li, L., Meroueh, S. O., Dunker, A. K., and Uversky, V. Analysis of structured and
intrinsically disordered regions of integral transmembrane proteins, Molecular Biosystems, 2009 in press.
Li, L., Liang, S., Pilcher, M. M., and Meroueh, S. O. Incorporating receptor flexibility in the molecular
design of protein interfaces, Protein Engineering Design and Selection,2009 22, 575-586.
Matute, J. D., Arias, A. A., Wright, N., Wrobel, I., Waterhouse, C. C. M., Li, X. J., Marchal, M. S.,
Stull, N. D., Lewis, D. B., Steele, M., Kellner, J. D., Yu, M., Meroueh, S. O., Nauseef, W. M., and
Dinauer, M. C. A new genetic subgroup of chronic granulomatous disease with defects in p40phox in a
box who presented with colitis, Blood, 2009114, 3309-3315.
Liang, S. D., Li, L. W., Hsu, W. L., Pilcher, M. N., Uversky, V., Zhou, Y. Q., Dunker, A. K., and
Meroueh, S. O.) Exploring the Molecular Design of Protein Interaction Sites with Molecular Dynamics
Simulations and Free Energy Calculations, Biochemistry 2009 48, 399-414.
Liang, S. D., Meroueh, S. O., Wang, G. C., Qiu, C., and Zhou, Y. Q. Consensus scoring for
enriching near-native structures from protein-protein docking decoys, Proteins-Structure
Function and Bioinformatics 2009 75, 397-403.
Shi, Q., Meroueh, S. O., Fisher, J. F., and Mobashery, S. Investigation of the mechanism
of the cell wall DD-carboxypeptidase reaction of penicillin-binding protein 5 of Escherichia
coli by quantum mechanics/molecular mechanics calculations, Journal of the American Chemical
Society 2008 130, 9293-9303.
Li, L., and Meroueh, S. O. (2008) Receptor-Ligand Interactions in Biological Systems, in
Encyclopedia for the Life Sciences, p 19, John Wiley and Sons, London.
L. Li, J. J. Dantzer, J. Nowacki, B. J. O?Callaghan and S. O. Meroueh "PDBcal: A
Comprehensive Dataset for Receptor-Ligand Interactions with Three-Dimensional Structures
and Binding Thermodynamics from Isothermal Titration Calorimetry" Chem. Biol. & Drug
Design. 2008, in press.
L. Li, N. V. Uversky, K. A. Dunker and S. O. Meroueh "A Computational Investigation of
Allostery in the Catabolite Activator Protein" J. Am. Chem. Soc. 2007, 129, 15668-15676.
G. Rosenblum, S. O. Meroueh, M. Toth, J. F. Fisher, R. Fridman, S. Mobashery and I. Sagi
"Molecular Structures and Dynamics of the Stepwise Activation of a Matrix
Metalloproteinase Zymogen: Challenging the Cysteine Switch Dogma" J. Am. Chem. Soc.
2007, 129, 13566-13574.
W. Zhang, Q. Shi, Q., S. O. Meroueh, S. B. Vakulenko and S. Mobashery "Catalytic
Mechanism of Penicillin-Binding Protein 5 of Escherichia coli." J. Biol. Chem. 2007, 46,
10113-10121.
S. O. Meroueh, S. Mobashery "Conformational Transition in the Aminoacyl t-RNA Site of
the Bacterial Robosome both in the Presence and Absence of an Aminoglycoside Antibiotic"
Chemical Biology & Drug Design 2007, 69, 291-297.
S. O. Meroueh, J. Cha, S. Mobashery "Inhibition of Class A Beta- Lactamases" in:
Enzyme-Mediated Resistance to Antibiotics: Mechanisms, Dissemination, and Prospects for
Inhibition, R. A. Bonomo and M. E. Tolmasky, Eds.; ASM Press: Washington, D. C., 2007,
pp 101-114.
S.
O. Meroueh, K. Z. Bencze, D. Hesek, M. Lee, J. F. Fisher, T. L.
Stemmler, S. Mobashery "Three-Dimensional Structure of the Bacterial
Cell Wall Peptidoglycan" Proc. Natl. Acad. Sci. USA
2006, 103, 4404-4409.
J. B. Murray, S. O. Meroueh, R. J. Russell, G. Lentzen, J. Haddad, S.
Mobashery "Interactions of Designer Antibiotics and the Bacterial
Ribosomal Aminoacyl-tRNA Site" Chem. Biol.
2006, 13, 129-38.
P. Osenkowski, S. O. Meroueh, D. Pavel, S. Mobashery, R. Fridman
"Mutational and Structural Analyses of the Hinge Region of Membrane
Type 1-Matrix Metalloproteinase and Enzyme Processing" J.
Biol. Chem. 2005, 280, 26160-26168.
S. O. Meroueh, J. F. Fisher, H. B. Schlegel, S. Mobashery "Ab initio
QM/MM Study of Class A Beta-Lactamase Acylation: Dual Participation of
Glu166 and Lys73 in a Concerted Base Promotion of Ser70" J.
Am. Chem. Soc. 2005, 127, 15397-15407.
M. Ikejiri, M. M. Bernardo, S. O. Meroueh, S. Brown, M. Chang, R.
Fridman, S. Mobashery "Design, Synthesis, and Evaluation of a
Mechanism-Based Inhibitor for Gelatinase A" J. Org.
Chem. 2005, 70, 5709-5712.
J. F. Fisher, S. O. Meroueh, S. Mobashery "Bacterial Resistance to
Beta-Lactam Antibiotics: Compelling Opportunism, Compelling
Opportunity" Chem. Rev. 2005, 105,
395-424.
J. B. Cross, T. Vreven, S. O. Meroueh, S. Mobashery, H. B. Schlegel
"Computational Investigation of Irreversible Inactivation of the
Zinc-Dependent Protease Carboxypeptidase A" J. Phys. Chem.
B 2005, 109, 4761-4769.
I. T. Lim, S. O. Meroueh, M. Lee, M. J. Heeg, S. Mobashery "Strategy
in Inhibition of Cathepsin B, A Target in Tumor Invasion and
Metastasis" J. Am. Chem. Soc. 2004, 126,
10271-10277.
D. Golemi-Kotra, S. O. Meroueh, C. Kim, S. B. Vakulenko, A. Bulychev,
A. J. Stemmler, T. L. Stemmler, S. Mobashery "The Importance of a
Critical Protonation State and the Fate of the Catalytic Steps in
Class A Beta-Lactamases and Penicillin-Binding Proteins" J.
Biol. Chem. 2004, 279, 34665-34673.
S. Brown, S. O. Meroueh, R. Fridman, S. Mobashery "Quest for
Selectivity in Inhibition of Matrix Metalloproteinases" Curr.
Top. Med. Chem. 2004, 4, 1227-1238.
G. Rosenblum, S. O. Meroueh, O. Kleifeld, S. Brown, S. P. Singson, R.
Fridman, S. Mobashery, I. Sagi "Structural Basis for Potent Slow
Binding Inhibition of Human Matrix Metalloproteinase-2 (MMP-2)"
J. Biol. Chem. 2003, 278, 27009-27015.
S. O. Meroueh, G. Minasov, W. Lee, B. K. Shoichet, S. Mobashery
"Structural Aspects for Evolution of Beta-Lactamases from
Penicillin-Binding Proteins" J. Am. Chem. Soc.
2003, 125, 9612-9618.
S. O. Meroueh, P. Roblin, D. Golemi, L. Maveyraud, S. B. Vakulenko, Y.
Zhang, J. P. Samama, S. Mobashery "Molecular Dynamics at the Root of
Expansion of Function in the M69L Inhibitor-Resistant TEM
Beta-Lactamase from Escherichia coli" J. Am. Chem.
Soc. 2002, 124, 9422-9430.
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