title: Combining structure-based drug design and pharmacophores.
abstract: Development towards integrated computer-aided drug design methodologies is presented by utilising crystal structure complexes to produce structure-based pharmacophores. These novel pharmacophores represent the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The protein-ligand complexes can also yield information about all interactions that ligands could potentially form with the binding site, as well as about the size of the binding cavity. Together, these describe a 'superligand', which can also be viewed as a pharmacophore. Various types of novel pharmacophores are discussed and compared, using HIV-1 reverse transcriptase (RT) as the target protein, and their application in database searching is presented.
authors.affiliation: School of Environmental and Life Sciences, University of Newcastle, NSW 2308, Australia. Renate.Griffith@newcastle.edu.au
authors.forename: Renate
authors.initials: R
authors.lastname: Griffith
authors.forename: Tien T T
authors.initials: TT
authors.lastname: Luu
authors.forename: James
authors.initials: J
authors.lastname: Garner
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
mesh_terms: D001665:Binding Sites; D017076:Computer-Aided Design; D030562:Databases, Protein; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008024:Ligands; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase