• • Program Description
  • SCBMB Curriculum
  • Training Support
  • About Houston
  Program
• • Executive Committee
  • Faculty
  • Students
  • Alumni
  • Staff
  People
• Affiliated Institutions
• • Centers and Institutes
  • Research Areas
  Research Opportunities
• Student Publications
• • Advanced Topics
  • Journal Club
  • Seminars
  • Retreats
  • Photo Album
  Events
• Directions
• Apply Here
• Intranet

Jim Briggs University of Houston Department: Department of Biology and Biochemistry Address: Dept. of Biology and Biochemistry, 5001 Houston Science Center, Room 402D University of Houston 4800 Calhoun Rd. Houston, TX 77204-5001 Phone: 713-743-8366 Fax: 713-743-8351 Email: jbriggs@uh.edu Web: adrik.bchs.uh.edu

Education

B.S. Chemistry, UT-El Paso (1984)
Ph.D. Theoretical Organic Chemistry, Purdue University (1990)
Postdoc. Chemistry, UH (1990-1994); Adjunct Asst. Prof. Pharmacology, UCSD (1994-1998)

Honors

Teaching Excellence Award, College of Natural Sciences and Mathematics, University of Houston 2004
Special Recognition for Outstanding Service to Students with 2000 Disabilities at the University of Houston
Oak Ridge Associated Universities New Faculty Development Award 1999-2000
Honorary Editorial Board Member, Open Access Bioinformatics, 2009-present

Honorary Editorial Board Member, Computational Biology and Chemistry: Advances and Applications, 2008-present

Associate Editor, PLoS Computational Biology, 2008-present

Editorial Advisory Board, Current Bioinformatics (journal), 2007-present

NIH/Molecular Structure and Function Study Section D (MSFD), Charter member, Jul07-Jun10

Research Topic

Computer-aided drug design; Molecular modeling; Computational biophysics

Research Description

Activities currently underway in my group involve the use and development of computer programs on high-performance computers to study the kinetic and thermodynamic properties of enzymes and receptors. Application areas include the search for inhibitors of the HIV-1 integrase (anti-AIDS), alanine racemases (anti-bacterial), botulinum and cholera toxins, analysis of the structural similarity of antimitotic/anticancer agents and their interactions with their binding site in beta-tubulin (anti-cancer), protein redesign, and more. Docking from 3D structural databases, molecular mechanics, molecular and Brownian dynamics, electrostatics, quantum mechanics, QSAR, and other methods are used in the work mentioned above.

The HIV-1 integrase splices the retroviral genome into the host DNA thereby hijacking the host cell machinery for making viral proteins. This enzyme, for which no good inhibitors are known, represents the third of the main enzyme targets in HIV. Work on this project is performed in collaboration with fourother research groups (X-ray crystallography, virology, organic synthesis, and marine biology) that represent a complete structure-based inhibitor design team. Our early results on this project are providing some clues about the structure of the active site. The initial small molecule docking studies have revealed hot spots for new functional group types that we are incorporating into newly designed lead compounds. A "dynamic" pharmacophore method has been developed which allows one to include protein flexibility during the inhibitor design process. Early results show that this approach is very promising, already leading to six initial inhibitor leads.

Other work underway in my group is also focused on enzymes that are targets for inhibitor design. Greater understanding of the reaction mechanism, structural dynamics, and of the effects of point mutations should lead to more rational design of next generation inhibitors for these enzymes that may be less prone to acquired resistance. All of these projects represent collaborations with one or more experimental groups.

Selected Publications

• Deng, J.; Lee, K. W.; Sanchez, T.; Cui, M.; Neamati, N.; Briggs, J. M. �Dynamic Receptor-Based Pharmacophore Model Development and its Application in Designing Novel HIV-1 Integrase Inhibitors�, J. Med. Chem., 2005, 48, 1496-1505.
• Brigo, A.; Lee, K. W.; Mustata, G. I.; Briggs, J. M. Comparative molecular dynamics simulations of HIV-1 integrase and the T66I/M154I mutant: binding modes and drug resistance to a diketo acid inhibitor�, Proteins: Str., Func., and Bioinf., 2005, 59, 723-741.
• Mustata, G. I.; Brigo, A.; Briggs, J. M. HIV-1 Integrase Pharmacophore Model Derived from Diverse Classes of Inhibitors�, Bioorg. Med. Chem. Lett., 2004, 14, 1447-1454.
• Adesokan, A. A.; Roberts, V. A.; Lee, K. W.; Lins, R. D.; Briggs, J. M. �Prediction of HIV-1 Integrase/viral DNA Interactions in the Catalytic Domain by Fast Molecular Docking�, J. Med. Chem., 2004, 47, 821-8.
• Lee, K. W.; Briggs, J. M. �Molecular Modeling Study of the Editing Active Site of Escherichia coli Leucyl-tRNA Synthetase: Two Amino Acid Binding Sites in the editing domain�, Proteins: Str. Function Bioinformatics, 2004, 54, 693-704.
• Mustata, G. I.; Briggs, J. M. �Cluster Analysis of Water Molecules in Alanine Racemase and their Putative Structural Role�, Protein Eng., Design, and Selection, 2004, 17, 223-234 (Cover).
• Barreca, M. L.; Lee, K. W.; Chimirri, A.; Briggs, J. M. �Molecular dynamics studies of the wild-type and double mutant HIV-1 integrase complexed with the 5CITEP inhibitor: mechanism for inhibition and drug resistance�, Biophys. J., 2003, 84, 1450-1463.
• Mandal, P. K.; Limbrick, D. W.; Coleman IV, D. R.; Dyer, G. A.; Ren, Z.; Sanderson Birtwistle, J.; Xiong, C.; Chen, X.; Briggs, J. M.; McMurray, J. S., “Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling”, J. Med. Chem., 2009, 52, 2429-42
• Joshi, M.; Ebalunode, J. O.; Briggs, J. M. “Computational insights into the interaction of the anthrax lethal factor with the N-terminal region of its substrates”, Proteins: Structure, Function, and Bioinformatics, 2009, 75, 323-35.
• Singh, N.; Briggs, J. M. “Molecular dynamics simulations of Factor Xa: Insight into conformational transitions in its binding subsites”, Biopolymers, 2008, 89, 1104-1113.
• Jawanda, N.; Ebalunode, J.; Gribenko, A.; Briggs J.; Ching Lee, J.; Tu, S.-C. “A Single-Residue Mutation Destabilizes Vibrio harveyi Flavin Reductase FRP Dimer”, Arch. Biochem. Biophys., 2008, 472, 51-57.
• Nunthaboot, N.; Pianwanit, S.; Parasuk, V.; Ebalunode, J. O.; Briggs, J. M.; Kokpol, S. “Hybrid Quantum Mechanical/Molecular Mechanical Simulations of HIV-1 Integrase/Inhibitor Complexes”, Biophys. J., 2007, 93, 3613-26.
• Fu, W.; Shen, J.; Luo, X.; Zhu, W.; Cheng, J.; Yu, K.; Briggs, J. M.; Jin, G.; Chen, K.; Jiang, J. “Dopamine D1 Receptor Agonist and D2 Receptor Antagonist Effects of the Natural Product (-)-Stepholidine (SPD): Molecular Modeling and Dynamics Simulations”, Biophys. J., 2007, 93, 1431-41. Zhai, Y.; Nawaz, M. H.; Lee, K. W.; Kirkbride, E.; Briggs, J. M.; Martinis, S. A. “Modulation of Substrate Specificity within the Amino Acid Editing Site of Leucyl-tRNA Synthetase”, Biochem., 2007, 46, 3331-3337.
• Nunthaboot, N.; Tonmunphean, S.; Parasuk, V.; Kokpol, S.; Briggs, J. M. “Computational studies of HIV-1 integrase and its inhibitors”, Curr. Comp.-Aided Drug Design, 2007, 214-233.
• Lee, K. W.; Kwon, Y. J.; Briggs, J. M. “Three Common Subunits in the Editing Domains of Class Ia tRNA Synthetases”, Bull. Korean Chem. Soc., 2007, 28, 207-210.
• Meltzer, R. H.; Thompson, E.; Soman, K.; Song X.-Z.; Ebalunode, J. O.; Wensel, T. G.; Briggs, J. M.; Pedersen, S. E. “Electrostatic Steering at Acetylcholine Binding Sites”, Biophys. J., 2006, 91, 1302-1314 (see also: New & Notable, Fairclough, R. H. “Recalled to Life: Resurrection of Diffusion-Enhanced Fluorescence Energy Transfer”, Biophys. J., 2006, 91, 1143-1144).
• Meltzer, R. H.; Villa-Carilles W.; Ebalunode, J. O.; Briggs, J. M.; Pedersen, S. E. “Computed Pore Potentials of the Nicotinic Acetylcholine Receptor”, Biophys. J., 2006, 91, 1325-1335 (see also: New & Notable, Fairclough, R. H. “Recalled to Life: Resurrection of Diffusion-Enhanced Fluorescence Energy Transfer”, Biophys. J., 2006, 91, 1143-1144).
• Deng, J.; Sanchez, T.; Neamati, N.; Briggs, J. M. “Dynamic Pharmacophore Model Optimization: Identification of Novel HIV-1 Integrase Inhibitors”, J. Med. Chem., 2006, 49, 1684-1692.
• Brigo, A.; Mustata, G. I.; Briggs, J. M.; Moro, S. “Discovery of HIV-1 Integrase Inhibitors through a Novel Combination of Ligand and Structure-based Drug Design”, Med. Chem., 2005, 1, 263-275.
• Mulder, B.; Anaya, S.; Yu, P.; Lee, K. W.; Nguyen, A.; Murphy, J.; Willson, R. C.; Briggs, J. M.; Gao, X.; Hardin, S. H. “Nucleotide Modification at the g-Phosphate Leads to the Improved Fidelity of HIV-1 Reverse Transcriptase”, Nucleic Acids Research, 2005, 33, 4865-4873.
• LeMagueres, P.; Im, H.; Ebalunode, J.; Strych, U.; Benedik, M. J.; Briggs, J. M.; Kohn, H. L.; Krause, K. L. “The 1.9 Å Crystal Structure of Alanine Racemase from Mycobacterium tuberculosis Contains a Conserved Entryway into the Active Site”, Biochem., 2005, 44, 1471-81.

Lab Members

Current Graduate Students
Former Grad Students
Current Post Docs
Former Post Docs

Lab Photos

Last edited on: July 23, 2009