title: Farnesyl diphosphate synthase inhibitors from in silico screening.
abstract: The relaxed complex scheme is an in silico drug screening method that accounts for receptor flexibility using molecular dynamics simulations. Here, we used this approach combined with similarity searches and experimental inhibition assays to identify several low micromolar, non-bisphosphonate inhibitors, bisamidines, of farnesyl diphosphate synthase (FPPS), an enzyme targeted by some anticancer and antimicrobial agents and for the treatment of bone resorption diseases. This novel class of farnesyl diphosphate synthase inhibitors have more drug-like properties than existing bisphosphonate inhibitors, making them interesting pharmaceutical leads.
authors: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA. slindert@ucsd.edu
authors: Steffen
authors: S
authors: Lindert
authors: Wei
authors: W
authors: Zhu
authors: Yi-Liang
authors: YL
authors: Liu
authors: Ran
authors: R
authors: Pang
authors: Eric
authors: E
authors: Oldfield
authors: J Andrew
authors: JA
authors: McCammon
mesh_terms: D000495:Allosteric Site; D019540:Area Under Curve; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D005663:Furans / Q000737:chemistry / Q000378:metabolism; D051228:Geranyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012372:ROC Curve
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; C469777:bisamidine; D051228:Geranyltranstransferase