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Jerome Baudry

Associate Professor

UT/ORNL


Research

The study of regulatory proteins within the human circulatory system that control a variety of processes, including formation/lysis of blood clots and aspects of humoral immunity and wound healing.

Description of Research

http://cmb.ornl.gov/people/baudry

The Baudry laboratory uses molecular modeling and computational chemistry to investigate how bio-molecules interact with each other. We are particularly interested in molecular discovery, i.e. how to select and/or design small molecules, like pharmaceuticals, that will interact in a specific and potent way with much larger molecules, like proteins. Small molecules may sometimes enhance, or sometimes inhibit, the functioning of the proteins to which they bind. To understand protein /ligand interactions we must know and understand a great deal about a particular protein, such as where are possible cavities in the protein, how do these cavities moves and change their shapes with time, and what are the side chains that define these cavities: are residues there neutral, charged, small, large, resonant etc? Molecular modeling allows such very detailed atomic-scale investigations. Drug discovery is the discovery and understanding of the atomic details that will allow small molecules to be perfectly happy, in a thermodynamic way, inside the binding sites of their target proteins. The Baudry lab is involved in structure-based molecular discovery on a variety of targets, such as cytochrome P450s, cancer targets, or hormone or antibiotic receptors, among others. In these projects we collaborate with various experimental groups to synthesize, screen, and test the small molecules for desired biological activity. In addition we are actively developing methods and protocols to accelerate computer-aided drug discovery and drug design.

We are also actively involved in a more fundamental approach to protein dynamics and ligand/protein interactions. We are investigating the dynamics of methyl groups in proteins and molecular crystals. Methyl groups, such as the side chain of alanine, are widely found in proteins and their rotations are very sensitive to the local microenvironment. Variation in methyl rotational dynamics is being recognized as a very important contribution to the thermodynamic of proteins and of protein/ligand interactions. We use theoretical methods to identify methyl groups in protein and molecular crystals that will undergo changes in their rotational dynamics upon ligand binding or micro-environmental variations, and we study how these changes are coupled with the functioning of the protein and the ligand binding. These studies have allowed us to extend our research in frontier domains such as solid-state and surface chemistry, and bio-nano technologies.


Education

  • PhD: Molecular Biophysics - University of Paris, Pierre and Marie Curie (Paris-06) (1997)

Publications

Ellingson SR, Miao Y, Baudry J, Smith JC. (2014) Multi-Conformer Ensemble Docking to Difficult Protein Targets. J Phys Chem B. 2014 Sep 24.

Ellingson SR, Smith JC, Baudry J. (2013) VinaMPI: facilitating multiple receptor high-throughput virtual docking on high-performance computers. J Comput Chem. 2013 Sep 30;34(25):2212-21.

Glass DC, Krishnan M, Smith JC, Baudry J. (2013) Three entropic classes of side chain in a globular protein. J Phys Chem B. 2013 Mar 21;117(11):3127-34. doi: 10.1021/jp400564q.

Active site hydration and water diffusion in cytochrome P450cam: a highly dynamic process. Y. Miao and J. Baudry (2011) Biophysical Journal. In Press

High-Throughput Virtual Molecular Docking: Hadoop Implementation of AutoDock4 on a Private Cloud. S.R. Ellingson and J. Baudry (2011) ECMLS 2011 Proceedings of the second international workshop on Emerging computational methods for the life sciences.

Three-dimensional mapping of micro-environmental control of methyl rotational barriers. W.I. Hembree and J. Baudry J Phys Chem B. (2011) 115(26), 8575-80

Arabidopsis thaliana NIP7;1: An Anther-Specific Boric Acid Transporter of the Aquaporin Superfamily Regulated by an Unusual Tyrosine in Helix 2 of the Transport Pore. T. Li, WG Choi, I.S. Wallace, J. Baudry, and D. M. Roberts Biochemistry (2011), 50(31), 6633?6641

A survey of aspartate-phenylalanine and glutamate-phenylalanine interactions in the protein data bank: searching for anion-pairs. V. Philip, J. Harris, R, Adams, D. Nguyen, J. Spiers, J. Baudry, E.E. Howell and R.J. Hinde. (2011) Biochemistry, 50(14), 2939-2950

Task-parallel MPI implementation of Autodock4 for docking of very large databases of compounds using High Performance Super-Computers B. Collignon, R.S. Schultz, J.C. Smith and J. Baudry J. Comput. Chem. (2011) 32(6), 1202?1209

Human TLRs 10 and 1 Share Common Mechanisms of Innate Immune Sensing but Not Signaling Y. Guan, D.R.E. Ranoa, S. Jiang,. S.K. Mutha, X. Li, J. Baudry, and R.I. Tapping Journal Immunol. (2010) 184: 5094?5103

Determinants of Catalytic Power and Ligand Binding in Glutamate Racemase. A.Spies, J.G. Reese, D. Dodd, K.L. Pankow, S.R. Blanke, and J. Baudry. J. Am. Chem. Soc. (2009) 15;131(14):5274-84.

Key Role of Active-Site Water Molecules in Bacteriorhodopsin Proton-Transfer Reactions. A.N. Bondar, J. Baudry, S. Suhai, S. Fischer, and J.C. Smith. J. Phys. Chem. B. 112, 14729-14741 (2008)

Biasing Reaction Pathways with Mechanical Force. C. R. Hickenboth, J.S. Moore, S.R. White, N. R. Sottos, J. Baudry Nature (2007) 446:423-427

van der Waals Interactions and Decrease of the Rotational Barrier of Methyl-size Rotators: A Theoretical Study. J. Baudry J. Am. Chem. Soc. (2006) 128(34):11088-11093

Class-Dependent Sequence Alignment Strategy Improves the Structural and Functional Modeling of P450s. J. Baudry, S. Rupasinghe, and M. Schuler Protein Eng. Des. Sel. (2006) 19(8):345?353

Can Proteins and Crystals Self-Catalyze Methyl Rotations? J. Baudry and J.C. Smith J. Phys. Chem. B. (2005) 109:20572-20578

Structure-based Design and In-Silico Virtual Screening of combinatorial Libraries. A Combined Chemical/Computational Assignment. J. Baudry and P. Hergenrother J. Chem. Edu. (2005) 82(6):890-894

Ile115Leu Mutation in the SRS1 Region of an Insect Cytochrome P450 (CYP6B1) Compromises Substrate Turnover via Changes in a Predicted Product Release Channel.Z. Wen, J. Baudry, M.R. Berenbaum, and M.A. Schuler Protein Eng. Des. Sel. (2005) 18(4):191-199

A Retinoic Acid Binding Cytochrome P450: CYP120A1 from Synechocystis sp. PCC 6803. N. Ke, J. Baudry, T. Makris, M. A. Schuler and S. G.Sligar Arch. Biochem. Biophys. (2005) 436:110-120


Contact Information

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