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Comparison of virtual high-throughput screening methods for the identification of phosphodiesterase-5 inhibitors
- Source :
- Journal of chemical information and modeling. 51(6)
- Publication Year :
- 2011
-
Abstract
- Reliable and effective virtual high-throughput screening (vHTS) methods are desperately needed to minimize the expenses involved in drug discovery projects. Here, we present an improvement to the negative image-based (NIB) screening: the shape, the electrostatics, and the solvation state of the target protein’s ligand-binding site are included into the vHTS. Additionally, the initial vHTS results are postprocessed with molecular mechanics/generalized Born surface area (MMGBSA) calculations to estimate the favorability of ligand-protein interactions. The results show that docking produces very good early enrichment for phosphodiesterase-5 (PDE-5); however, in general, the NIB and the ligand-based screening performed better with or without the added electrostatics. Furthermore, the postprocessing of the NIB screening results using MMGBSA calculations improved the early enrichment for the PDE-5 considerably, thus, making hit discovery affordable.
- Subjects :
- Cyclic Nucleotide Phosphodiesterases, Type 5
Virtual screening
High-Throughput Screening Methods
Drug discovery
Chemistry
General Chemical Engineering
High-throughput screening
Medical screening
Static Electricity
Drug Evaluation, Preclinical
Nanotechnology
General Chemistry
Computational biology
Library and Information Sciences
Molecular Dynamics Simulation
Phosphodiesterase 5 Inhibitors
Ligands
Computer Science Applications
High-Throughput Screening Assays
Substrate Specificity
User-Computer Interface
Docking (molecular)
Catalytic Domain
Subjects
Details
- ISSN :
- 1549960X
- Volume :
- 51
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of chemical information and modeling
- Accession number :
- edsair.doi.dedup.....a444e3ef120e2042209b289ee0f4fda4