ArticleCommunications chemistry2018
Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo.
Article in Communications chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed.
- Structural Basis for BD1-Preferring 2,4-Disubstituted Pyrimidine BRDT Inhibitors.Journal of medicinal chemistry · 2026Article
- Water Networks as Hydrophobic Recognition Motifs in Proteins.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Thermodynamics of Water Displacement from Binding Sites and its Contributions to Supramolecular and Biomolecular Affinity.Angewandte Chemie (International ed. in English) · 2025Article
- Binding-Site Purification of Actives (B-SPA) Enables Efficient Large-Scale Progression of Fragment Hits by Combining Multi-Step Array Synthesis With HT Crystallography.Angewandte Chemie (International ed. in English) · 2025Article
- Modeling Ligand Binding Site Water Networks with Site Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities.Journal of chemical theory and computation · 2024Article
- Identification of novel bromodomain inhibitors ofAntimicrobial agents and chemotherapy · 2024Article
- Article
- The role of loop dynamics in the prediction of ligand-protein binding enthalpy.Chemical science · 2023Article
- Accounting for Solvation Correlation Effects on the Thermodynamics of Water Networks in Protein Cavities.Journal of chemical information and modeling · 2023Article
- Water Networks in Complexes between Proteins and FDA-Approved Drugs.Journal of chemical information and modeling · 2023Article
- Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33α and TRIM33β Bromodomains.ACS chemical biology · 2022Article
- SAMPL7 protein-ligand challenge: A community-wide evaluation of computational methods against fragment screening and pose-prediction.Journal of computer-aided molecular design · 2022Article
- Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.Journal of chemical theory and computation · 2022Article
- A Structure-based Design Approach for Generating High Affinity BRD4 D1-Selective Chemical Probes.Journal of medicinal chemistry · 2022Article
- Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks [Article v0.1].Living journal of computational molecular science · 2022Article
- Design and Synthesis of LM146, a Potent Inhibitor of PB1 with an Improved Selectivity Profile over SMARCA2.ACS omega · 2021Article
- Discovery of a hidden transient state in all bromodomain families.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Selective N-Terminal BET Bromodomain Inhibitors by Targeting Non-Conserved Residues and Structured Water Displacement*.Angewandte Chemie (International ed. in English) · 2021Article
- Comparing Fragment Binding Poses Prediction Using HSP90 as a Key Study: When Bound Water Makes the Difference.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Conserved water molecules are of interest in drug design, as displacement of such waters can lead to higher affinity ligands and in some cases, contribute towards selectivity. Bromodomains, small protein domains involved in the epigenetic regulation of gene transcription, display a network of four conserved water molecules in their binding pockets and have recently been the focus of intense medicinal chemistry efforts. Understanding why certain bromodomains have displaceable water molecules and others do not is extremely challenging, and it remains unclear which water molecules in a given bromodomain can be targeted for displacement. Here we estimate the stability of the conserved water molecules in 35 bromodomains via binding free energy calculations using all-atom grand canonical Monte Carlo simulations. Encouraging quantitative agreement to the available experimental evidence is found. We thus discuss the expected ease of water displacement in different bromodomains and the implications for ligand selectivity.
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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.