ArticleJournal of chemical information and modeling2012
Protein flexibility in virtual screening: the BACE-1 case study.
Article in Journal of chemical information and modeling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer's Disease: From In Silico to In Vivo.International journal of molecular sciences · 2022Article
- L-DOPA and Droxidopa: From Force Field Development to Molecular Docking into Human βLife (Basel, Switzerland) · 2022Article
- Analysis of L-DOPA and droxidopa binding to human βBiophysical journal · 2021Article
- Energy penalties enhance flexible receptor docking in a model cavity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting the C-Terminal Domain Small Phosphatase 1.Life (Basel, Switzerland) · 2020Review
- Novel K-Ras G12C Switch-II Covalent Binders Destabilize Ras and Accelerate Nucleotide Exchange.Journal of chemical information and modeling · 2018Article
- Changing Paradigm from one Target one Ligand Towards Multi-target Directed Ligand Design for Key Drug Targets of Alzheimer Disease: An Important Role of In Silico Methods in Multi-target Directed Ligands Design.Current neuropharmacology · 2018Article
- The Development of Target-Specific Pose Filter Ensembles To Boost Ligand Enrichment for Structure-Based Virtual Screening.Journal of chemical information and modeling · 2017Article
- DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites.Journal of medicinal chemistry · 2016Article
- Computational protein-ligand docking and virtual drug screening with the AutoDock suite.Nature protocols · 2016Article
- Ultra-High-Throughput Structure-Based Virtual Screening for Small-Molecule Inhibitors of Protein-Protein Interactions.Journal of chemical information and modeling · 2016Article
- Discovery of Novel ROCK1 Inhibitors via Integrated Virtual Screening Strategy and Bioassays.Scientific reports · 2015Article
- DOCK 6: Impact of new features and current docking performance.Journal of computational chemistry · 2015Article
- Theory and applications of covalent docking in drug discovery: merits and pitfalls.Molecules (Basel, Switzerland) · 2015Review
- AutoDock4(Zn): an improved AutoDock force field for small-molecule docking to zinc metalloproteins.Journal of chemical information and modeling · 2014Article
- Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery.Nature chemistry · 2014Article
- Article
- Integration of ligand-based drug screening with structure-based drug screening by combining maximum volume overlapping score with ligand docking.Pharmaceuticals (Basel, Switzerland) · 2012Article
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Authors and funding
10 authors.
Funding
Abstract
Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secretase inhibitors. To this aim, we incorporated protein flexibility in our simulations by using an ensemble of static X-ray enzyme structures to screen the National Cancer Institute database. A unified description of the protein motion was also generated by computing and combining a set of grid maps using an energy weighting scheme. Such a description was used in an energy-weighted virtual screening experiment on the same molecular database. Assessment of the enrichment factors from these two virtual screening approaches demonstrated comparable predictive powers, with the energy-weighted method being faster than the ensemble method. The in vitro evaluation demonstrated that out of the 32 tested ligands, 17 featured the predicted enzyme inhibiting property. Such an impressive success rate (53.1%) demonstrates the enhanced power of the two methodologies and suggests that energy-weighted virtual screening is a more than valid alternative to ensemble virtual screening given its reduced computational demands and comparable performance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.