title: Fragment screening and HIV therapeutics.
abstract: Fragment screening has proven to be a powerful alternative to traditional methods for drug discovery. Biophysical methods, such as X-ray crystallography, NMR spectroscopy, and surface plasmon resonance, are used to screen a diverse library of small molecule compounds. Although compounds identified via this approach have relatively weak affinity, they provide a good platform for lead development and are highly efficient binders with respect to their size. Fragment screening has been utilized for a wide range of targets, including HIV-1 proteins. Here, we review the fragment screening studies targeting HIV-1 proteins using X-ray crystallography or surface plasmon resonance. These studies have successfully detected binding of novel fragments to either previously established or new sites on HIV-1 protease and reverse transcriptase. In addition, fragment screening against HIV-1 reverse transcriptase has been used as a tool to better understand the complex nature of ligand binding to a flexible target.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bauman
authors.forename: Disha
authors.initials: D
authors.lastname: Patel
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000627:therapeutic use*; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D019380:Anti-HIV Agents; D054852:Small Molecule Libraries; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1