Abstract

Understanding the evolution of drug resistance in HIV-1 protease necessitates a molecular-leveldescription of protein variants and small molecule (drug) interactions. The Structure and Modeling Core willprovide structural information for retroviral proteases and their small molecule complexes as required by thefour Projects. The Core will perform service-oriented structural and computational studies, using proventechniques of x-ray crystallographic analysis, computational docking, and rational drug design. Dr. Goodsellwill direct the structural modeling and docking analysis of mutant enzymes and their complexes, based oncrystal structures and extending analysis to all mutants and potential inhibitors as identified in the individualProjects. Dr. Stout will direct the crystallographic structure determination of retroviral proteases and theircomplexes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
1P01GM083658-01
Application #
7434200
Study Section
Special Emphasis Panel (ZRG1-AARR-A (40))
Project Start
2008-02-18
Project End
2012-11-30
Budget Start
2008-02-18
Budget End
2008-11-30
Support Year
1
Fiscal Year
2008
Total Cost
$194,129
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Khamaikawin, Wannisa; Saoin, Somphot; Nangola, Sawitree et al. (2015) Combined Antiviral Therapy Using Designed Molecular Scaffolds Targeting Two Distinct Viral Functions, HIV-1 Genome Integration and Capsid Assembly. Mol Ther Nucleic Acids 4:e249
Routh, Andrew; Chang, Max W; Okulicz, Jason F et al. (2015) CoVaMa: Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data. Methods 91:40-47
Tiefendbrunn, Theresa; Stout, C David (2014) Towards novel therapeutics for HIV through fragment-based screening and drug design. Prog Biophys Mol Biol 116:124-40
Tiefenbrunn, Theresa; Forli, Stefano; Happer, Meaghan et al. (2014) Crystallographic fragment-based drug discovery: use of a brominated fragment library targeting HIV protease. Chem Biol Drug Des 83:141-8
Tsai, Yingssu; McPhillips, Scott E; González, Ana et al. (2013) AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery. Acta Crystallogr D Biol Crystallogr 69:796-803
Lin, Ying-Chuan; Happer, Meaghan; Elder, John H (2013) Selection of drug-resistant feline immunodeficiency virus (FIV) encoding FIV/HIV chimeric protease in the presence of HIV-specific protease inhibitors. J Virol 87:8524-34
Chang, Max W; Oliveira, Glenn; Yuan, Jinyun et al. (2013) Rapid deep sequencing of patient-derived HIV with ion semiconductor technology. J Virol Methods 189:232-4
Breuer, Sebastian; Espinola, Sheryll; Morelli, Xavier et al. (2013) A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction. Curr Chem Genom Transl Med 7:16-20
Tiefenbrunn, Theresa; Forli, Stefano; Baksh, Michael M et al. (2013) Small molecule regulation of protein conformation by binding in the Flap of HIV protease. ACS Chem Biol 8:1223-31
Joshi, Pheroze; Sloan, Barbara; Torbett, Bruce E et al. (2013) Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores. Virology 436:162-72

Showing the most recent 10 out of 28 publications