ArticleNature chemistry2014
Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery.
Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 154 citations in OpenAlex.
- Improving AlphaFold2 Performance in Virtual Screens Targeting GPCRs by Enhancing Binding-Site Conformational Sampling.Journal of chemical information and modeling · 2026Article
- Benchmarking co-folding methods to predict the structures of covalent protein-ligand complexes.Acta pharmacologica Sinica · 2026Article
- Unfreezing structural biology for drug discovery.Nature chemical biology · 2026Review
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Comparative Structural Analysis of Escherichia Coli Cyay at Room and Cryogenic Temperatures Using Macromolecular and Serial Crystallography.Chembiochem : a European journal of chemical biology · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- The impact of library size and scale of testing on virtual screening.Nature chemical biology · 2025Article
- Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning.Science advances · 2025Article
- Article
- Virtual fragment screening for DNA repair inhibitors in vast chemical space.Nature communications · 2025Article
- Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.Journal of chemical information and modeling · 2025Article
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
- Reliability of AlphaFold2 Models in Virtual Drug Screening: A Focus on Selected Class A GPCRs.International journal of molecular sciences · 2024Article
- AlphaFold and Protein Folding: Not Dead Yet! The Frontier Is Conformational Ensembles.Annual review of biomedical data science · 2024Review
- The impact of Library Size and Scale of Testing on Virtual Screening.bioRxiv : the preprint server for biology · 2024Article
- Toward physics-based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants.Protein science : a publication of the Protein Society · 2024Review
- Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP.Communications biology · 2024Article
- Considerations Around Structure-Based Drug Discovery for KRAS Using DOCK.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cell phenotypes can be predicted from propensities of protein conformations.Current opinion in structural biology · 2023Review
- Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.Biomolecules · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Proteins fluctuate between alternative conformations, which presents a challenge for ligand discovery because such flexibility is difficult to treat computationally owing to problems with conformational sampling and energy weighting. Here we describe a flexible docking method that samples and weights protein conformations using experimentally derived conformations as a guide. The crystallographically refined occupancies of these conformations, which are observable in an apo receptor structure, define energy penalties for docking. In a large prospective library screen, we identified new ligands that target specific receptor conformations of a cavity in cytochrome c peroxidase, and we confirm both ligand pose and associated receptor conformation predictions by crystallography. The inclusion of receptor flexibility led to ligands with new chemotypes and physical properties. By exploiting experimental measures of loop and side-chain flexibility, this method can be extended to the discovery of new ligands for hundreds of targets in the Protein Data Bank for which similar experimental information is available.
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.