Ronald Levy Professor Rutgers University Chemistry Dept. Wright-Rieman Labs Piscataway. NJ 08855 (732) 445-3947 FAX - 5312 ronlevy@lutece.rutgers.edu

Protein structure. dynamics. and folding statistical thermodynamics of solutions protein electrostatics. ligand binding. and docking structural genomics large scale software development for molecular modeling

We use a combination of computer simulations. statistical mechanics and modeling. to study the structure. function. folding. and dynamics of proteins in solution. Current research projects concern problems in the statistical thermodynamics of solutions. protein electrostatics and ligand binding. protein dynamics on longer time scales. and large scale software development for molecular modeling. We are interested in the interplay between computational models and experiments at different levels of resolution. We have begun a new research project in the area of Computational Molecular Biology; more specifically in the emerging field of Structural Genomics. Better integration of protein sequence and structural information is a central aim of this work. We hope to develop computational tools which will be useful for predicting the functions of newly sequenced genes as well as for studying the basic physical principles of protein folding.

Selected Publications

Felts, A.K., Andrec, M., Gallicchio, E. and R.M. Levy. Protein Folding and Binding: Effective Potentials, Replica Exchange Simulations, and Network Models, in "Water and Biomolecules - Physical Chemistry of Life Phenomena", Springer Science (2008).

Felts, A.K., Gallicchio, E., Chekmarev, D., Paris, K.A., Friesner, R.A. and Levy, R.M. (2008). Prediction of protein loop conformations Using the AGBNP implicit solvent model and torsion angle sampling. J. Chem. Theor. Comput. 4:855-858.

Weinstock DS, Narayanan C, Baum J, Levy RM. (2008) Correlation between 13Calpha chemical shifts and helix content of peptide ensembles. Protein Sci. 17(5):950-4.

Knight JL, Zhou Z, Gallicchio E, Himmel DM, Friesner RA, Arnold E, Levy RM. (2008) Exploring structural variability in X-ray crystallographic models using protein local optimization by torsion-angle sampling. Acta Crystallogr D Biol Crystallogr. 64(Pt 4):383-96.

Zheng W, Andrec M, Gallicchio E, Levy RM. (2008) Simple continuous and discrete models for simulating replica exchange simulations of protein folding. J Phys Chem B. 112(19):6083-93.

Gallicchio E, Levy RM, Parashar M. (2008) Asynchronous replica exchange for molecular simulations. J Comput Chem. 29(5):788-94.

Zheng W, Andrec M, Gallicchio E, Levy RM. (2007) Simulating replica exchange simulations of protein folding with a kinetic network model. Proc Natl Acad Sci U S A. 104(39):15340-5.

Andrec, M., D.A. Snyder, Z. Zhou, J. Young, G.T. Montelione, and R.M. Levy. (2007) A large data set comparison of protein structures determined by crystallography and NMR: Statistical test for structural differences and the effect of crystal contacts. Proteins. 69(3):449-65.

Su, Y., E. Gallicchio, K. Das, E. Arnold, and R.M. Levy. (2007) Linear interaction energy (LIE) models for ligand binding in implicit solvent: Theory and application to the binding of NNRTIs to HIV-1 reverse transcriptase. J. Chem. Theory Comput. 3:256-277.

Ravindranathan, K.P., E. Gallicchio, A.E. McDermott, and R.M. Levy. (2007) Conformational dynamics of substrate in the active site of cytochrome P450 BM-3/NPG complex: Insights from NMR order parameters. J. Am. Chem. Soc. 129:474-475.

Weinstock, D.S., C. Narayanan, A.K. Felts., M. Andrec, R.M. Levy, K-P. Wu., and J. Baum. (2007). Distinguishing among structural ensembles of the GB1 peptide: REMD simulations and NMR experiments. J. Am. Chem. Soc. 129:4858-4859.

Himmel, D.M., S.G. Sarafianos, S. Dharmasena, M. M. Hossain, K. McCoy-Simandle, T. Ilina, A.D. Clark, Jr., J.L. Knight, J.G. Julias, P.K. Clark, K. Krogh-Jespersen, R.M. Levy, S.H. Hughes, M.A. Parniak, and E. Arnold. (2006). HIV-1 reverse transcriptase structure with RNase H inhibitor DHBNH bound at a novel site. ACS Chem. Biol. 1:702-712.

Ravindranathan KP. Gallicchio E. Friesner RA. McDermott AE. Levy RM. (2006) Conformational equilibrium of cytochrome P450 BM-3 complexed with N-palmitoylglycine: a replica exchange molecular dynamics study. J Am Chem Soc. 128(17):5786-91.

Banks JL. Beard HS. Cao Y. Cho AE. Damm W. Farid R. Felts AK. Halgren TA. Mainz DT. Maple JR. Murphy R. Philipp DM. Repasky MP. Zhang LY. Berne BJ. Friesner RA. Gallicchio E. Levy RM. (2005) Integrated Modeling Program. Applied Chemical Theory (IMPACT). J Comput Chem. 26(16):1752-80.

Ravindranathan KP. Gallicchio E. Levy RM. (2005) Conformational equilibria and free energy profiles for the allosteric transition of the ribose-binding protein. J Mol Biol. 353(1):196-210.

Andrec M. Felts AK. Gallicchio E. Levy RM. (2005) Protein folding pathways from replica exchange simulations and a kinetic network model. Proc Natl Acad Sci U S A. 102(19):6801-6.

Andrec M. Kholodenko BN. Levy RM. Sontag E. (2005) Inference of signaling and gene regulatory networks by steady-state perturbation experiments: structure and accuracy. J Theor Biol. 232(3):427-41.

Knight JL. Mekler V. Mukhopadhyay J. Ebright RH. Levy RM. (2005) Distance-restrained docking of rifampicin and rifamycin SV to RNA polymerase using systematic FRET measurements: developing benchmarks of model quality and reliability. Biophys J. 88(2):925-38.

Mukhopadyay, J., E. Sineva, J. Knight, R.M. Levy, and R.H. Ebright. (2004). Antibacterial Peptide Microsin J25 (MCCJ25) Inhibits Transcription by Binding Within, and Obstructing, the RNA Polymerase Secondary Channel. Molecular Cell 14:739-751.

Felts. A.K.. Harano. Y.. Gallicchio. E.. Levy. R.M. (2004) Free energy surfaces of beta-hairpin and alpha-helical peptides generated by replica exchange molecular dynamics with the AGNP implicit solvent model. Proteins. 56(2):310-21.

Gallicchio E.. and Levy. R.M. (2004) AGBNP. an analytic implicit solvent model suitable for molecular dynamics simulations and high-resolution modeling. J Comput Chem. 25(4):479-99.

Du. P.. Andrec. M. and Levy. R.M. (2003). Have we seen all structures corresponding to short protein fragments in the Protein Data Bank? An update. Protein Engineering 16:407-414.

Levy. R.M.. Zhang. L.Y.. Gallicchio. E. and Felts. A.K. (2003). On the non-polar hydration free energy of proteins: Surface area and continuum solvent models for the solute-solvent interaction energy. J. Am. Chem Soc. 125:9523-9530.

Andrec. M. . Levy. R.M. and Talaga. D. (2003). Direct determination of kinetic rates from single molecule photon arrival trajectories using hidden Markov models. Journal of Physical Chemistry A. 107:7454-7464.

Gallicchio. E.. Zhang. L.Y. and Levy. R.M. (2002) The SGB/NP model for the solvent potential of mean force in water based on the surface generalized born model and a non-polar hydration free energy estimator. J. Comp. Chem. 23:517-529.

Wallqvist. A.. Gallicchio. E.. Felts. A.K. and Levy. R.M. (2002). Detecting native protein folds among large decoy sets with the OPLS all-atom potential and surface generalized born solvent model. in "Computational Methods for Protein Folding: A Special Volume of Advances in Chemical Physics. " Vol. 120. R. Friesner. editor. I. Prigogine and S.A. Rice. series editors. John Wiley & Sons. 459-486.

Andrec. M.. and Levy. R.M. (2002). Protein sequential resonance assignments by combinatorial enumeration using 13 C-alpha chemical shifts and their (i. i-1) sequential connectivities.J. Biomolecular NMR 23:263-270.

Andrec. M.. Harano. Y.. Jacobson. M.P.. Friesner. R.A. and Levy. R.M. (2002). Complete protein structure determination using backbone residual dipolar couplings and sidechain Rotamer Prediction Journal of Structural and Functional Genomics 2:103-111.

Mekler. V.. Kortkhonjia. E.. Mukhopadhyay. J.. Knight. J.. Revyakin. A.. Kapanidis. A.N. . Niu. W.. Ebright. Y.W.. Levy. R. and Ebright. R.H. (2002) Structural organization of bacterial RNA Polymerase Holoenzyme and the RNA Polymerase-promoter open complex. Cell 108:599-614.

Felts. A.K.. Gallicchio. E.. Wallqvist. A. and Levy. R.M. (2002).Distinguishing native conformations of proteins from decoys with an effective free energy estimator based on the OPLS all-atom force field and the surface generalized born solvent model Proteins 48:404-422.

Kubo. M.. Levy.. R.M. . Rossky. P.J. . Matubayasi. N. and Nakahara. M. (2002). Chloride ion hydration and diffusion in supercritical water using a polarizable water model. J. Phys. Chem. 106:3979-3986.

Andrec. M.. Du. P. and Levy. R.M. (2001) Protein backbone structure determination using only residual dipolar couplings from one ordering medium. J. Biomol. NMR 21:335-347.

Zhou. R.. Friesner. R.A.. Ghosh. A.. Rizzo. R.C.. Jorgensen. W.L. and Levy. R.M. (2001) New linear interaction method for binding affinity calculations using a continuum solvent model. J. Phys. Chem.105:10388-10397.

Wallqvist. A.. Gallicchio. E. and Levy. R.M. (2001). A model for studying drying at hydrophobic interfaces: Structural and thermodynamic properties. J. Phys. Chem 105:6745-6753.

Andrec. M.. Du. P. and Levy. R.M. (2001). Protein structural motif recognition via NMR residual dipolar couplings. J. Am. Chem. Soc 123:1222-1229.

Goodfellow. J.. and Levy. R.M.. (2000). Theory and simulation: Editorial overview. Current Opinion in Structural Biology 10:137-138.

Zhang. L.. Gallicchio. E.. Friesner. R. and Levy. R.M. (2001). Solvent models for protein-ligand binding: Comparison of implicit solvent poisson and surface generalized born models with explicit solvent simulations. J. Comp. Chem 22:591-607.

Andrec. M.. Montelione. G.T. and Levy. R.M.. (2000). Lipari-Szabo mapping: A graphical approach to Lipari-Szabo analysis of NMR relaxation data using reduced spectral density mapping. J. Biomolecular NM 18:83-100.