Jerome Baudry, Ph.D.
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Molecular modeling and computational molecular biophysics of protein/ligand interactions and of protein structure/function relationship
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.
Y. Miao and J. Baudry (2011) Active site hydration and water diffusion in cytochrome P450cam: a highly dynamic process. Biophysical Journal. In Press
High-Throughput Virtual Molecular Docking: Hadoop Implementation of AutoDock4 on a Private Cloud. S.R. Ellingson and J. Baudry. Concurrency andComputation: Practice and Experience. In Press. (Baudry Corresponding author; Ellingson GST graduate student)
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. Tian Li, Won-Gyu Choi, Ian S. Wallace, Jerome Baudry, and Daniel M. Roberts. Biochemistry, 2011, 50 (31), pp 6633–6641
Three-dimensional mapping of micro-environmental control of methyl rotational barriers. W.I. Hembree and J. Baudry J Phys Chem B. 2011 Jul 7;115(26):8575-80 (Baudry corresponding author; Hembree undergraduate student)
A survey of aspartate-phenylalanine and glutamate-phenylalanine
interactions in the protein data bank: searching for anion-p pairs.
V. Phillips, J. Harris, R, Adams, D. Nguyen, J. Spiers, J. Baudry, E.E. Howell and R.J. Hinde. Biochemistry, (2011) 50 (14):2939-2950
(Spiers undergraduate in Baudry's lab; Harris GST graduate student in Baudry's lab)
Task-parallel message passing interface implementation of Autodock4
for docking of very large databases of compounds using high-performance
super-computers. B. Collignon, R. Schulz, J.C. Smith and J. Baudry.
J. Comput. Chem. (2011) 32 (6): 1202–1209 (Baudry corresponding author; Collignon Post-doc in Baudry's lab and Smith's lab)
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) 131 (14): 5274–5284
Biasing Reaction Pathways with Mechanical Force. C. R. Hickenboth, J.S. Moore, S.R. White, N. R. Sottos, J. Baudry, and S.R. Wilson 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):345ñ353
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
Jerome Baudry, Ph.D.
UT/ORNL Center for Molecular Biophysics
Oak Ridge National Laboratory
Oak Ridge, TN 37830
Phone: (865) 576 0930