ArticleJournal of cheminformatics2014
Experimental validation of FINDSITE(comb) virtual ligand screening results for eight proteins yields novel nanomolar and micromolar binders.
Article in Journal of cheminformatics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- Differential kinase activity of ACVR1 G328V and R206H mutations with implications to possible TβRI cross-talk in diffuse intrinsic pontine glioma.Scientific reports · 2020Article
- Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs.Medicinal research reviews · 2019Review
- FINDSITEJournal of chemical information and modeling · 2018Article
- Pocket detection and interaction-weighted ligand-similarity search yields novel high-affinity binders for Myocilin-OLF, a protein implicated in glaucoma.Bioorganic & medicinal chemistry letters · 2017Article
- Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants.ACS chemical biology · 2017Article
- On the importance of composite protein multiple ligand interactions in protein pockets.Journal of computational chemistry · 2017Article
- Why Is There a Glass Ceiling for Threading Based Protein Structure Prediction Methods?The journal of physical chemistry. B · 2017Article
- Repurposing FDA-approved drugs for anti-aging therapies.Biogerontology · 2016Article
- Novel small molecule binders of human N-glycanase 1, a key player in the endoplasmic reticulum associated degradation pathway.Bioorganic & medicinal chemistry · 2016Article
- Catalytic and substrate promiscuity: distinct multiple chemistries catalysed by the phosphatase domain of receptor protein tyrosine phosphatase.The Biochemical journal · 2016Article
- How special is the biochemical function of native proteins?F1000Research · 2016Review
- Modeling enzyme-ligand binding in drug discovery.Journal of cheminformatics · 2015Review
- Ligand binding studies, preliminary structure-activity relationship and detailed mechanistic characterization of 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine derivatives as inhibitors of Escherichia coli dihydrofolate reductase.European journal of medicinal chemistry · 2015Article
- PoLi: A Virtual Screening Pipeline Based on Template Pocket and Ligand Similarity.Journal of chemical information and modeling · 2015Article
- Comprehensive prediction of drug-protein interactions and side effects for the human proteome.Scientific reports · 2015Article
- Template-based prediction of protein function.Current opinion in structural biology · 2015Review
- Article
- Implications of the small number of distinct ligand binding pockets in proteins for drug discovery, evolution and biochemical function.Bioorganic & medicinal chemistry letters · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundIdentification of ligand-protein binding interactions is a critical step in drug discovery. Experimental screening of large chemical libraries, in spite of their specific role and importance in drug discovery, suffer from the disadvantages of being random, time-consuming and expensive. To accelerate the process, traditional structure- or ligand-based VLS approaches are combined with experimental high-throughput screening, HTS. Often a single protein or, at most, a protein family is considered. Large scale VLS benchmarking across diverse protein families is rarely done, and the reported success rate is very low. Here, we demonstrate the experimental HTS validation of a novel VLS approach, FINDSITE(comb), across a diverse set of medically-relevant proteins.
resultsFor eight different proteins belonging to different fold-classes and from diverse organisms, the top 1% of FINDSITE(comb)'s VLS predictions were tested, and depending on the protein target, 4%-47% of the predicted ligands were shown to bind with μM or better affinities. In total, 47 small molecule binders were identified. Low nanomolar (nM) binders for dihydrofolate reductase and protein tyrosine phosphatases (PTPs) and micromolar binders for the other proteins were identified. Six novel molecules had cytotoxic activity (<10 μg/ml) against the HCT-116 colon carcinoma cell line and one novel molecule had potent antibacterial activity.
conclusionsWe show that FINDSITE(comb) is a promising new VLS approach that can assist drug discovery.
Indexed as
Identifiers
What OpenQuestion holds
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.