Farnesyl Diphosphate Synthase Inhibitors from In Silico Screening
Open Access
- 19 February 2013
- journal article
- research article
- Published by Wiley in Chemical Biology & Drug Design
- Vol. 81 (6), 742-748
- https://doi.org/10.1111/cbdd.12121
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.Keywords
This publication has 33 references indexed in Scilit:
- Non‐Bisphosphonate Inhibitors of Isoprenoid Biosynthesis Identified via Computer‐Aided Drug DesignChemical Biology & Drug Design, 2011
- NNScore: A Neural-Network-Based Scoring Function for the Characterization of Protein−Ligand ComplexesJournal of Chemical Information and Modeling, 2010
- Targeting Isoprenoid Biosynthesis for Drug Discovery: Bench to BedsideAccounts of Chemical Research, 2010
- AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreadingJournal of Computational Chemistry, 2009
- AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibilityJournal of Computational Chemistry, 2009
- Lipophilic Bisphosphonates as Dual Farnesyl/Geranylgeranyl Diphosphate Synthase Inhibitors: An X-ray and NMR InvestigationJournal of the American Chemical Society, 2009
- Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast CancerNew England Journal of Medicine, 2009
- An improved relaxed complex scheme for receptor flexibility in computer-aided drug designJournal of Computer-Aided Molecular Design, 2008
- PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulationsNucleic Acids Research, 2007
- PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculationsNucleic Acids Research, 2004