ArticleNature communications2018
Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 245 citations in OpenAlex.
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- The Role of Water in Protein-Ligand Binding: Decisive Factor, Annoying Feature, or Indispensable Control Element: In Any Case, a Major Challenge.ChemMedChem · 2026Article
- Chemical composition and insecticidal activity of Salvia rosmarinus 'Eretto Liguria' essential oil against tomato leaf miner (Tuta absoluta).Scientific reports · 2026Article
- Advances of 3D microcrystals electron diffraction for transmembrane protein structure determination.Biophysical journal · 2026Review
- Molecular Scale Hydrophobicity and Adsorption Thermodynamics on Hydrophobic-Charged Surfaces.ACS nano · 2026Article
- Thermodynamic Data Remain a Hot Tip for Decoding Binding Affinity and Water Impact on Protein-Ligand Complex Formation to Assist Lead Optimization.Journal of medicinal chemistry · 2026Review
- A hypomorphic SRD5A2 haplotype with a potential founder effect: composed of common variants in individuals with 5α-reductase type 2 deficiency from South China.Biology of sex differences · 2026Article
- A highly dynamic mononuclear non-heme iron enzyme for the two-step isonitrile biosynthesis.Nature communications · 2026Article
- Water Networks as Hydrophobic Recognition Motifs in Proteins.Angewandte Chemie (International ed. in English) · 2026Article
- WatCon: A Python Tool for Analysis of Conserved Water Networks Across Protein Families.JACS Au · 2025Article
- Superwater as a generative AI framework to predict water molecule positions on protein structures.Communications chemistry · 2025Article
- A highly active Burkholderia polyketoacyl-CoA thiolase for production of triacetic acid lactone.Nature communications · 2025Article
- Visualize Transient Water-Mediated Hydrogen Bonds Facilitating the Formation of Enzymatic Near-Attack Conformers.JACS Au · 2025Article
- Evaluating the ciprofloxacin potentiation efficacy of repurposed drug flupentixol through efflux pump inhibition of pathogenic bacteria.Scientific reports · 2025Article
- Undirected Exploration of Binding Pockets with Flexible Topology.Journal of chemical theory and computation · 2025Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydrogen bonds are key interactions determining protein-ligand binding affinity and therefore fundamental to any biological process. Unfortunately, explicit structural information about hydrogen positions and thus H-bonds in protein-ligand complexes is extremely rare and similarly the important role of water during binding remains poorly understood. Here, we report on neutron structures of trypsin determined at very high resolutions ≤1.5 Å in uncomplexed and inhibited state complemented by X-ray and thermodynamic data and computer simulations. Our structures show the precise geometry of H-bonds between protein and the inhibitors N-amidinopiperidine and benzamidine along with the dynamics of the residual solvation pattern. Prior to binding, the ligand-free binding pocket is occupied by water molecules characterized by a paucity of H-bonds and high mobility resulting in an imperfect hydration of the critical residue Asp189. This phenomenon likely constitutes a key factor fueling ligand binding via water displacement and helps improving our current view on water influencing protein-ligand recognition.
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