Assistant Professor Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
Health Information and Translational Sciences Building
410 W. 10th Street, HS 5000
Indianapolis, Indiana 46202-3011 Phone: (317) 274-8315
Facsimile: (317) 274-4686
E-mail: smeroueh@iupui.edu
CCBB Web site
Chemistry Web Site

Ph.D., 2001, Wayne State University
Post Doctoral, 2001-2003, Wayne State University
Post Doctoral, 2003-2006, University of Notre Dame

Area of Study

Molecular Design and Characterization of Small Molecules that Target Protein Interactions and Enzymes in Cancer and Neurological Disorders.  More details...

Selected Recent Publications (>60)

Zhang, Q., Zeng, S. X., Zhang, Y., Zhang, Y., Meroueh, S. O. and Lu, Hua (2011) A Small Molecule Inauzhing Inhibits SIRT1 Activity and Suppresses Tumor Growth via Activation of p53, EMBO J., submitted

Khanna, M., Wang, F., Jo, I., Li, Liwei, Bum-Erdene, K., Li, J., Wang, B., Khanna, R., and Meroueh, S. O., (2011) Targeting Multiple Conformations Leads to a Small Molecule Inhibitors of the uPAR·uPA Protein-Protein Interaction that Blocks Cancer Cell Invasion, ACS Chem. Biol., In press PDF

Wang, F., Li. J., Sinn, A.L., Knabe, W. C., Khanna, May, Jo, I., Silver, J. M., Oh, K., Li, L., Sandusky,G. E., Sledge, G. W., Nakshatri, H., Jones, D. R., Pollok, K. E., Meroueh, S.O. (2011) Virtual Screening Targeting the Urokinase Receptor, Biochemical and Cell-Based Studies, Synthesis, Pharmacokinetic Characterization, and Effect on Breast Tumor Metastasis, J. Med. Chem., In press, PDF

Brittain, J.M., D.B. Duarte, S.M. Wilson, Z. Weiguo, C. Ballard, P.L. Johson, N. Liu, B. Xiong, M.S. Ripsch, Y. Wang, J.C. Fehrenbacher, S.D. Fitz, M. Khanna, C.-K. Park, B.S. Schmutzler, B.M. Cheon, M.R. Due, T. Brustovetsky, N. Ashpole, A. Hudmon, S.O. Meroueh, C.M. Hingtgen, N. Brustovetsky, R.-R. Ji, J.H. Hurley, X. Jin, A. Shekhar, X.-M. Xu, G. Oxford, M.R. Vasko, F.A. White, and R. Khanna, Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca2+ channel complex. Nature Medicine, 2011: in press, PDF

Li .L., Wang. B., and Meroueh, S. O. (2011) Support Vector Machine Scoring of Receptor-Ligand Complexes for Virtual Screening of Chemical Libraries, J. Chem. Inf. and Model., In press, PDF

Shi, Q., Meroueh, S. O., Fisher, J. F., and Mobashery S. (2011) A Computational Evaluation of the Mechanism of Penicillin Binding Protein Catalyzed Cross-linking of the Bacterial Cell Wall, Journal of the American Chemical Society, 133(14):5274-83, PDF

Khanna, M., Chelladurai, B., Gavini, A., Li, L., Shao, M., Courtney, D., Turchi,J. J., Matei, D., and Meroueh, S. O. (2011) Targeting Ovarian Tumor Cell Adhesion Mediated by Tissue Transglutaminase, Mol. Cancer Ther., 10(4):626-36, PDF

Li, L., Khanna, M., Jo, I., Wang, F. and Meroueh, S. O. (2011) Target-Specific Support Vector Machine Scoring in Structure-Based Virtual Screening:  Computational Validation, in Vitro Testing in Kinases, and Effects on Lung Cancer Cell Proliferation. J. Chem. Inf. and Model., 51(4):755-9, PDF

Wang, Y., Brittain, J. M., Jarecki, B. W., Park, K. D., Wilson, S. M., Hale, R., May Khanna, M., Ashpole, N. M., Meroueh, S. O., Cummins, T. R., and Khanna, R., (2010) In silico docking and electrophysiological characterization of lacosamide binding sites on collapsin response mediator protein 2 (CRMP-2) identifies a pocket important in modulating sodium channel slow inactivation.  Journal of Biological Chemistry, 285, 25296-307.PDF

Li, L., J. Li, M. Khanna, I. Jo, J.P. Baird, and Meroueh, S. O. (2010) Docking to Erlotinib Off-Targets Leads to Inhibitors of Lung Cancer Cell Proliferation with Suitable in Vitro Pharmacokinetics. ACS Med. Chem. Lett.  1, 229-233. PDF

Li, L.; Bumerdene, K.; Baenziger, P. H.; Hemmert, J. R.; Rosen, J.; Nellis, J.; Pierce, M. ; Meroueh, S. O. (2010) BioDrugScreen:  A Computational Drug Design Resource for Ranking Molecules Docked to the Human Proteome, Nucleic Acid Research, 38, D765-73. PDF

Xue, B., Oldfield, C., Li, L., Meroueh, S. O., Dunker, A. K., and Uversky, V. (2009) Analysis of structured and intrinsically disordered regions of integral transmembrane proteins, Molecular Biosystems, 5,1688-1702. PDF

Li, L., Liang, S., Pilcher, M. M., and Meroueh, S. O. (2009) Incorporating receptor flexibility in the molecular design of protein interfaces, Protein Engineering Design and Selection, 22, 575-86. PDF

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. (2009) A new genetic subgroup of chronic granulomatous disease with defects in p40phox in a box who presented with colitis, Blood, 114, 3309. PDF

Liang, S. D., Li, L. W., Hsu, W. L., Pilcher, M. N., Uversky, V., Zhou, Y. Q., Dunker, A. K., and Meroueh, S. O. (2009) Exploring the Molecular Design of Protein Interaction Sites with Molecular Dynamics Simulations and Free Energy Calculations, Biochemistry 48, 399-414. PDF

Liang, S. D., Meroueh, S. O., Wang, G. C., Qiu, C., and Zhou, Y. Q. (2009) Consensus scoring for enriching near-native structures from protein-protein docking decoys, Proteins-Structure Function and Bioinformatics 75, 397-403. PDF

Shi, Q., Meroueh, S. O., Fisher, J. F., and Mobashery, S. (2008) 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 130, 9293-9303. PDF

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.

Li, L., Dantzer, J. J., Nowacki, J., O'Callaghan, B. J., and Meroueh, S. O. (2008) PDBcal: a comprehensive dataset for receptor-ligand interactions with three-dimensional structures and binding thermodynamics from isothermal titration calorimetry, Chemical biology & drug design 71, 529-532. PDF

Jewell, J. L., Oh, E., Bennett, S. M., Meroueh, S. O., and Thurmond, D. C. (2008) The Tyrosine Phosphorylation of Munc18c Induces a Switch in Binding Specificity from Syntaxin 4 to Doc2{beta}, The Journal of biological chemistry 283, 21734-21746. PDF

Li, L., Uversky, V. N., Dunker, A. K., and Meroueh, S. O. (2007) A computational investigation of allostery in the catabolite activator protein, Journal of the American Chemical Society 129, 15668-15676. PDF

Zhang, W. L., Shi, Q. C., Meroueh, S. O., Vakulenko, S. B., and Mobashery, S. (2007) Catalytic mechanism of penicillin-binding protein 5 of Escherichia coli, Biochemistry 46, 10113-10121. PDF

Rosenblum, G., Meroueh, S., Toth, M., Fisher, J. F., Fridman, R., Mobashery, S., and Sagi, I. (2007) Molecular structures and dynamics of the stepwise activation mechanism of a matrix metalloproteinase zymogen: Challenging the cysteine switch dogma, Journal of the American Chemical Society 129, 13566-13574. PDF

Meroueh, S. O., and Mobashery, S. (2007) Conformational transition in the aminoacyl t-RNA site of the bacterial ribosome both in the presence and absence of an aminoglycoside antibiotic, Chemical biology & drug design 69, 291-297. PDF

Rekharsky, M., Hesek, D., Lee, M., Meroueh, S. O., Inoue, Y., and Mobashery, S. (2006) Thermodynamics of interactions of vancomycin and synthetic surrogates of bacterial cell wall, Journal of the American Chemical Society 128, 7736-7737. PDF

Rahaman, A., Song, H., Wang, A. X., Meroueh, S. O., and Hase, W. L. (2006) Chemical Dynamics Simulations of Energy Transfer and Unimolecular Decomposition in Collision-Induced Dissociation (CID) and Surface-Induced Dissociation (SID), in Principles of Mass Spectrometry Applied to Biomolecules (Litschitz, C., and Laskin, J., Eds.), pp 379-432, Wiley, New York.

Murray, J. B., Meroueh, S. O., Russell, R. J. M., Lentzen, G., Haddad, J., and Mobashery, S. (2006) Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site, Chemistry & biology 13, 129-138. PDF

Meroueh, S. O., Bencze, K. Z., Hesek, D., Lee, M., Fisher, J. F., Stemmler, T. L., and Mobashery, S. (2006) Three-dimensional structure of the bacterial cell wall peptidoglycan, P Natl Acad Sci USA 103, 4404-4409. PDF

Fisher, J. F.; Meroueh, S. O.; Mobashery, S., (2006) Nanomolecular and Supramolecular Paths toward the Bacterial Peptidoglycan Structure. Microbe, 1, 420-427. PDF

Hesek, D., Toth, M., Meroueh, S. O., Brown, S., Zhao, H., Sakr, W., Fridman, R., and Mobashery, S. (2006) Design and characterization of a metalloproteinase inhibitor-tethered resin for the detection of active MMPs in biological samples, Chemistry & biology 13, 379-386. PDF

Toth, M., Osenkowski, P., Hesek, D., Brown, S., Meroueh, S., Sakr, W., Mobashery, S., and Fridman, R. (2005) Cleavage at the stem region releases an active ectodomain of the membrane type 1 matrix metalloproteinase, Biochemical Journal 387, 497-506.

Osenkowski, P., Meroueh, S. O., Pavel, D., Mobashery, S., and Fridman, R. (2005) Mutational and structural analyses of the hinge region of membrane type 1-matrix metalloproteinase and enzyme processing, Journal of Biological Chemistry 280, 26160-26168. PDF

Meroueh, S. O., Fisher, J. F., Schlegel, H. B., and Mobashery, S. (2005) Ab initio QM/MM study of class A beta-lactamase acylation: Dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70, Journal of the American Chemical Society 127, 15397-15407.

Li, J., Cross, J. B., Vreven, T., Meroueh, S. O., Mobashery, S., and Schlegel, H. B. (2005) Lysine carboxylation in proteins: OXA-10 beta-lactamase, Proteins-Structure Function and Bioinformatics 61, 246-257. PDF

Lee, M., Bernardo, M. M., Meroueh, S. O., Brown, S., Fridman, R., and Mobashery, S. (2005) Synthesis of chiral 2-(4-phenoxyphenylsulfonylmethyl)thiiranes as selective gelatinase inhibitors, Organic letters 7, 4463-4465.

Ikejiri, M., Bernardo, M. M., Meroueh, S. O., Brown, S., Chang, M., Fridman, R., and Mobashery, S. (2005) Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A, J Org Chem 70, 5709-5712.

Fisher, J. F., Meroueh, S. O., and Mobashery, S. (2005) Bacterial resistance to beta-lactam antibiotics: Compelling opportunism, compelling opportunity, Chem Rev 105, 395-424.

Cross, J. B., Vreven, T., Meroueh, S. O., Mobashery, S., and Schlegel, H. B. (2005) Computational investigation of irreversible inactivation of the zinc-dependent protease carboxypeptidase A, J Phys Chem B 109, 4761-4769.

Lim, I. T., Meroueh, S. O., Lee, M., Heeg, M. J., and Mobashery, S. (2004) Strategy in inhibition of cathepsin B, A target in tumor invasion and metastasis, Journal of the American Chemical Society 126, 10271-10277.

Kim, C., Haddad, J., Vakulenko, S. B., Meroueh, S. O., Wu, Y., Yan, H., and Mobashery, S. (2004) Fluorinated aminoglycosides and their mechanistic implication for aminoglycoside 3 '-phosphotransferases from Gram-negative bacteria, Biochemistry 43, 2373-2383.

Golemi-Kotra, D., Meroueh, S. O., Kim, C., Vakulenko, S. B., Bulychev, A., Stemmler, A. J., Stemmler, T. L., and Mobashery, S. (2004) The importance of a critical protonation state and the fate of the catalytic steps in class A beta-lactamases and penicillin-binding proteins, Journal of Biological Chemistry 279, 34665-34673.

Brown, S., Meroueh, S. O., Fridman, R., and Mobashery, S. (2004) Quest for selectivity in inhibition of matrix metalloproteinases, Current topics in medicinal chemistry 4, 1227-1238.

Birck, C., Cha, J. Y., Cross, J., Schulze-Briese, C., Meroueh, S. O., Schlegel, H. B., Mobashery, S., and Samama, J. P. (2004) X-ray crystal structure of the acylated beta-lactam sensor domain of BlaR1 from Staphylococcus aureus and the mechanism of receptor activation for signal transduction, Journal of the American Chemical Society 126, 13945-13947.

Wilkinson, A. S., Bryant, P. K., Meroueh, S. O., Page, M. G. P., Mobashery, S., and Wharton, C. W. (2003) A dynamic structure for the acyl-enzyme species of the antibiotic aztreonam with the Citrobacter freundii beta-lactamase revealed by infrared spectroscopy and molecular dynamics simulations, Biochemistry 42, 1950-1957.

Wang, J. P., Meroueh, S. O., Wang, Y. F., and Hase, W. L. (2003) Efficiency of energy transfer in protonated diglycine and dialanine SID - Effects of collision angle, peptide ion size, and intramolecular potential, International Journal of Mass Spectrometry 230, 57-64.

Song, K. Y., Meroueh, O., and Hase, W. L. (2003) Dynamics of Cr(CO)(6)(+) collisions with hydrogenated surfaces, J Chem Phys 118, 2893-2902.

Rosenblum, G., Meroueh, S. O., Kleifeld, O., Brown, S., Singson, S. P., Fridman, R., Mobashery, S., and Sagi, I. (2003) Structural basis for potent slow binding inhibition of human matrix metalloproteinase-2 (MMP-2), Journal of Biological Chemistry 278, 27009-27015.

Meroueh, S. O., Minasov, G., Lee, W., Shoichet, B. K., and Mobashery, S. (2003) Structural aspects for evolution of beta-lactamases from penicillin-binding proteins, Journal of the American Chemical Society 125, 9612-9618.

Golemi-Kotra, D., Cha, J. Y., Meroueh, S. O., Vakulenko, S. B., and Mobashery, S. (2003) Resistance to beta-lactam antibiotics and its mediation by the sensor domain of the transmembrane BlaR signaling pathway in Staphylococcus aureus, Journal of Biological Chemistry 278, 18419-18425.

Fridman, R., Toth, M., Chvyrkova, I., Meroueh, S. O., and Mobashery, S. (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B), Cancer Metast Rev 22, 153-166.

Research Interests

Research in my laboratory is centered on using three dimensional structure of proteins targets to design small molecules that modulate their function.  These small molecules serve as chemical probes to study these targets in their native environment either in cell culture or in vivo, and in some cases provide leads for the development of therapeutic agents in cancer and neurological disorders.  Our work currently focuses on the following classes of targets:  urokinase-type plasminogen activator system, serine/threonine kinases, aldehyde dehydrogenases, and voltage-gated calcium channels.  Compounds are identified through structure-based design that involves molecular docking and scoring.  While we rely on existing docking methods, we develop new approaches to accurately score complexes and rank compounds.  Structure-activity relationship studies that we carry out provides valuable data to guide the design of next generation compounds and to improve our structure-based drug design methods. Initially, compounds are acquired from commercial sources and tested for activity in biochemical and cell culture-based assays that we develop.  Promising molecules as well as their derivatives are synthesized and further evaluated for activity.  Some compounds are eventually assessed for efficacy in animal studies through collaborations.