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Last Updated: 06/17/15

Computational Drug Development Group (CDDG)


The Computational Drug Development Group provides computational support to NeXT/CBC, Division, DTP, and joint CCR/DCTD projects. CDDG’s capabilities include a variety computational chemistry and biology techniques.

  • Protein Structure Modeling
  • Quantum Mechanics (Ab initio & DFT)
  • Structure-based Discovery and Design
  • Pharmacophore Modeling & Molecular Docking
  • Functional Biology
  • Systems Biology & Pathway Prediction
  • Bioinformatics and Chemoinformatics

CDDG Personnel

Name Role Email
CAPT Rick Gussio PhD Section Chief
Brian D. Peyser PhD Computational Biology
Connor McGrath PhD Bioinformatics
James C. Burnett PhD Structural Medicinal Chemistry
Ann R. Hermone PhD Computational Chemistry

Selected Publications

  1. Kiris, E., Burnett, J.C., Nuss, J.E., Wanner, L.M., Peyser, B.D., Du, H.T., Gomba, G.Y., Kota, K.P., Panchal, R.G., Gussio, R., Kane, C.D., Tessarollo, L., Bavari, S., 2015. SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons. Neurotox Res 27, 384–398.
  2. Salamoun, J., Anderson, S., Burnett, J.C., Gussio, R., Wipf, P., 2014. Synthesis of heterocyclic triads by Pd-catalyzed cross-couplings and evaluation of their cell-specific toxicity profile. Org Lett 16, 2034–2037.
  3. Mathews Griner, L.A., Guha, R., Shinn, P., Young, R.M., Keller, J.M., Liu, D., Goldlust, I.S., Yasgar, A., McKnight, C., Boxer, M.B., Duveau, D.Y., Jiang, J.-K., Michael, S., Mierzwa, T., Huang, W., Walsh, M.J., Mott, B.T., Patel, P., Leister, W., Maloney, D.J., Leclair, C.A., Rai, G., Jadhav, A., Peyser, B.D., Austin, C.P., Martin, S.E., Simeonov, A., Ferrer, M., Staudt, L.M., Thomas, C.J., 2014. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells. Proc Natl Acad Sci U S A 111, 2349–2354.
  4. dos Santos, E. d.A., Hamel, E., Bai, R., Burnett, J.C., Tozatti, C.S.S., Bogo, D., Perdomo, R.T., Antunes, A.M.M., Marques, M.M., Matos, M. d.F.C., de Lima, D.P., 2013. Synthesis and evaluation of diaryl sulfides and diaryl selenide compounds for antitubulin and cytotoxic activity. Bioorg Med Chem Lett 23, 4669–4673.
  5. Kota, K.P., Eaton, B., Lane, D., Ulrich, M., Ulrich, R., Peyser, B.D., Robinson, C.G., Jaissle, J.G., Pegoraro, G., Bavari, S., Panchal, R.G., 2013. Integrating high-content imaging and chemical genetics to probe host cellular pathways critical for Yersinia pestis infection. PLoS One 8, e55167.
  6. Hermone, A.R., Gussio, R., 2013. Calculation methods for the enhancement of pharmaceutical properties in small molecules: estimating the cationic pKa. Curr Pharm Des 19, 4310–4315.
  7. Sarkar, T., Nguyen, T.L., Su, Z.-W., Hao, J., Bai, R., Gussio, R., Qiu, S.X., Hamel, E., 2012. Interaction of pseudolaric acid B with the colchicine site of tubulin. Biochem Pharmacol 84, 444–450.
  8. Nguyen, T.L., Cera, M.R., Pinto, A., Lo Presti, L., Hamel, E., Conti, P., Gussio, R., De Wulf, P., 2012. Evading Pgp activity in drug-resistant cancer cells: a structural and functional study of antitubulin furan metotica compounds. Mol Cancer Ther 11, 1103–1111.
  9. Chen, D.Y., Lee, Y., Van Tine, B.A., Searleman, A.C., Westergard, T.D., Liu, H., Tu, H.-C., Takeda, S., Dong, Y., Piwnica-Worms, D.R., Oh, K.J., Korsmeyer, S.J., Hermone, A., Gussio, R., Shoemaker, R.H., Cheng, E.H.-Y., Hsieh, J.J.-D., 2012. A pharmacologic inhibitor of the protease Taspase1 effectively inhibits breast and brain tumor growth. Cancer Res 72, 736–746.
  10. Bai, R., Nguyen, T.L., Burnett, J.C., Atasoylu, O., Munro, M.H.G., Pettit, G.R., Smith, 3rd, A.B., Gussio, R., Hamel, E., 2011. Interactions of halichondrin B and eribulin with tubulin. J Chem Inf Model 51, 1393–1404.
  11. Nguyen, T.L., Xu, X., Gussio, R., Ghosh, A.K., Hamel, E., 2010. The assembly-inducing laulimalide/peloruside a binding site on tubulin: molecular modeling and biochemical studies with [3H]peloruside A. J Chem Inf Model 50, 2019–2028.
  12. Screpanti, E., Santaguida, S., Nguyen, T., Silvestri, R., Gussio, R., Musacchio, A., Hamel, E., De Wulf, P., 2010. A screen for kinetochore-microtubule interaction inhibitors identifies novel antitubulin compounds. PLoS One 5, e11603.
  13. Gussio, R., Currens, M.J., Scudiero, D.A., Smith, J.A., Lannigan, D.A., Shoemaker, R.H., Zaharevitz, D.W., Nguyen, T.L., 2010. RSK2 Binding Models Delineate Key Features for Activity. J Chem Pharm Res 2, 587–598.
  14. Burnett, J.C., Wang, C., Nuss, J.E., Nguyen, T.L., Hermone, A.R., Schmidt, J.J., Gussio, R., Wipf, P., Bavari, S., 2009. Pharmacophore-guided lead optimization: the rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease. Bioorg Med Chem Lett 19, 5811–5813.
  15. Wilcox, E., McGrath, C., Blokhin, A.V., Gussio, R., Hamel, E., 2009. Evidence for a distinct ligand binding site on tubulin discovered through inhibition by GDP of paclitaxel-induced tubulin assembly in the absence of exogenous GTP. Arch Biochem Biophys 484, 55–62.
  16. Hermone, A.R., Burnett, J.C., Nuss, J.E., Tressler, L.E., Nguyen, T.L., Solaja, B.A., Vennerstrom, J.L., Schmidt, J.J., Wipf, P., Bavari, S., Gussio, R., 2008. Three-dimensional database mining identifies a unique chemotype that unites structurally diverse botulinum neurotoxin serotype A inhibitors in a three-zone pharmacophore. ChemMedChem 3, 1905–1912.
  17. Burnett, J.C., Ruthel, G., Stegmann, C.M., Panchal, R.G., Nguyen, T.L., Hermone, A.R., Stafford, R.G., Lane, D.J., Kenny, T.A., McGrath, C.F., Wipf, P., Stahl, A.M., Schmidt, J.J., Gussio, R., Brunger, A.T., Bavari, S., 2007. Inhibition of metalloprotease botulinum serotype A from a pseudo-peptide binding mode to a small molecule that is active in primary neurons. J Biol Chem 282, 5004–5014.
  18. Burnett, J.C., Opsenica, D., Sriraghavan, K., Panchal, R.G., Ruthel, G., Hermone, A.R., Nguyen, T.L., Kenny, T.A., Lane, D.J., McGrath, C.F., Schmidt, J.J., Vennerstrom, J.L., Gussio, R., Solaja, B.A., Bavari, S., 2007. A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease. J Med Chem 50, 2127–2136.
  19. Nguyen, T.L., McGrath, C., Hermone, A.R., Burnett, J.C., Zaharevitz, D.W., Day, B.W., Wipf, P., Hamel, E., Gussio, R., 2005. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J Med Chem 48, 6107–6116.
  20. McGrath, C.F., Pattabiraman, N., Kellogg, G.E., Lemcke, T., Kunick, C., Sausville, E.A., Zaharevitz, D.W., Gussio, R., 2005. Homology model of the CDK1/cyclin B complex. J Biomol Struct Dyn 22, 493–502.
  21. Nguyen, T.L., McGrath, C., Hermone, A.R., Burnett, J.C., Zaharevitz, D.W., Day, B.W., Wipf, P., Hamel, E., Gussio, R., 2005. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J Med Chem 48, 6107–6116.
  22. Burnett, J.C., Schmidt, J.J., McGrath, C.F., Nguyen, T.L., Hermone, A.R., Panchal, R.G., Vennerstrom, J.L., Kodukula, K., Zaharevitz, D.W., Gussio, R., Bavari, S., 2005. Conformational sampling of the botulinum neurotoxin serotype A light chain: implications for inhibitor binding. Bioorg Med Chem 13, 333–341.
  23. Burnett, J.C., Schmidt, J.J., Stafford, R.G., Panchal, R.G., Nguyen, T.L., Hermone, A.R., Vennerstrom, J.L., McGrath, C.F., Lane, D.J., Sausville, E.A., Zaharevitz, D.W., Gussio, R., Bavari, S., 2003. Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity. Biochem Biophys Res Commun 310, 84–93.
  24. Gussio, R., Zaharevitz, D.W., McGrath, C.F., Pattabiraman, N., Kellogg, G.E., Schultz, C., Link, A., Kunick, C., Leost, M., Meijer, L., Sausville, E.A., 2000. Structure-based design modifications of the paullone molecular scaffold for cyclin-dependent kinase inhibition. Anticancer Drug Des 15, 53–66.
  25. Gussio, Fojo, Giannakakou, 2000. Reply. Trends Pharmacol Sci 21, 323–324.
  26. Giannakakou, P., Gussio, R., Nogales, E., Downing, K.H., Zaharevitz, D., Bollbuck, B., Poy, G., Sackett, D., Nicolaou, K.C., Fojo, T., 2000. A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells.. Proc Natl Acad Sci U S A 97, 2904–2909.