Combining structure-based drug design and pharmacophores.
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.
Griffith
Renate
R
School of Environmental and Life Sciences, University of Newcastle, NSW 2308, Australia. Renate.Griffith@newcastle.edu.au
Luu
Tien T T
TT
Garner
James
J
Keller
Paul A
PA
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
D008024:Ligands; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase