James Briggs, Ph.D.
Associate Professor, Biology & Biochemistry
University of Houston
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)
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 four other 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 Dr. Briggs' 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.
- Mallipeddi PL, Joshi M and Briggs JM. Pharmacophere based virtual screening to aid in the identification of unknown protein function. Chem Biol Drug Des, 80(6):828-42 (2012). PubMed
- Zhu H and Briggs JM. Mechanistic role of NS4A and substrate in the activation of HCV NS3 protease. Proteins, 79(8):2428-43 (2011). PubMed
- Mandal PK, Limbrick D, Coleman DR, Dyer GA, Ren Z, Birtwistile JS, Xiong C, Chen X, Briggs JM and McMurray JS. Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling. J Med Chem, 52(8):2429-42, (2009). PubMed
- Joshi M, Ebalunode JO and Briggs JM. Computational insights into the interaction of the anthrax lethal factor with the N-terminal region of its substrates. Proteins, 75(2):323-35 (2009). PubMed
- Singh N and Briggs JM. Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites. Biopolymers, 89(12):1104-13 (2008). PubMed
- Zhai Y, Nawaz MH, Lee KW, Kirkbride E, Briggs JM and Martinis SA. Modulation of substrate specificity within the amino acid editing site of leucyl-tRNA synthetase. Biochemistry, 46(11):3331-7 (2007). PubMed
- Meltzer RH Vila-Carriles W, Ebalunode JO, Briggs JM and Pedersen SE. Computed pore potentials of the nicotinic acetylcholine receptor. Biophys J, 91(4):1325-35 (2006). PubMed
For more publications, see listing on PubMed.
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
Additional Links: University of Houston