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Protein structure. dynamics. and folding statistical thermodynamics of solutions protein electrostatics. ligand binding. and docking structural genomics large scale software development for molecular modelingWe 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 PublicationsGallicchio E, Levy RM. (2011) Advances in all atom sampling methods for
modeling protein-ligand binding affinities. Curr Opin Struct Biol. Feb
19. [Epub ahead of print] Lapelosa, M., Ferstandig Arnold, G., Gallicchio, E., Arnold, E. and Levy, R.M. (2010) Antigenic characteristics of rhinovirus chimeras designed in silico for enhanced presentation of HIV-1 gp41 epitopes. J Mol Biol. Apr 2;397(3):752-66. Erratum in: J Mol Biol. May 14;398(4):623-4. Okumura, H., Gallicchio, E. and Levy, R.M. (2010) Conformational populations of ligand-sized molecules by replica exchange molecular dynamics and temperature reweighting. J Comput Chem. May;31(7):1357-67. Gallicchio, E., Paris, K. and Levy, R.M. (2009). The AGBNP2 implicit solvent model. J. Chem. Theory & Comput 5:2544-2564. Haq, O., Levy, R.M., Morozov, A.V. and Andrec, M. (2009). Pairwise and higher-order correlations among drug-resistance mutations in HIV-1 subtype B protease. BMC Bioinformatics 10(Suppl 8):S10. Wu, K-P, Weinstock, D.S., Narayanan, C., Levy, R.M. and Baum, J. (2009). Structural reorganization of α-synuclein at low pH observed by NMR and REMD simulations. J. Mol. Biol. 391:784-796. Zheng, W., Andrec, M., Gallicchio, E. and Levy, R.M. (2009). Recovering kinetics from a simplified protein folding model using replica exchange simulations: A kinetic network and effective stochastic dynamics. J. Phys. Chem. B 113:11702-11709. Paris, K.A., Haq, O., Felts, A.K., Das, K., Arnold, E. and Levy, R.M. (2009). Conformational landscape of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Non-Nucleoside Inhibitor Binding Pocket: Lessons for inhibitor design from a cluster analysis of many crystal structures. J. Med. Chem. 52:6413-6420. Lapelosa M, Gallicchio E, Arnold GF, Arnold E, Levy RM. (2009) In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes. J Mol Biol. 385(2):675-91. 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. |
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