ArticleJournal of chemical information and modeling2018
Prediction of Ordered Water Molecules in Protein Binding Sites from Molecular Dynamics Simulations: The Impact of Ligand Binding on Hydration Networks.
Article in Journal of chemical information and modeling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Predicting water at the protein interface in cryo-EM structures from MD-excess chemical potential.Biophysical journal · 2026Article
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- Water-Based Pharmacophore Modeling in Kinase Inhibitor Design: A Case Study on Fyn and Lyn Protein Kinases.Journal of chemical information and modeling · 2025Article
- Understanding the HIV-CA protein and the ligands that bind at the N-terminal domain (NTD) - C-terminal domain (CTD) interface.RSC medicinal chemistry · 2025Review
- Fused pyrido[3,4-D]pyrimidine moiety with phthalazinone ring accelerate dual inhibition of PARP1 and CDK4 in triple-negative breast cancer: a hybrid design with computational investigation through molecular modeling and quantum mechanics.Journal of molecular modeling · 2025Article
- De Novo Hydration of Cryo-EM Reconstructions through Molecular Dynamics Simulations of the Excess Chemical Potential.bioRxiv : the preprint server for biology · 2025Article
- Unveiling polyphenol-protein interactions: a comprehensive computational analysis.Journal of cheminformatics · 2025Article
- Unveiling the Anticancer Potential: Computational Exploration of Nitrogenated Derivatives of (+)-Pancratistatin as Topoisomerase I Inhibitors.International journal of molecular sciences · 2024Article
- Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.ACS omega · 2024Article
- Deciphering Molecular Aspects of PotentialMetabolites · 2023Article
- Article
- LAWS: Local alignment for water sites-Tracking ordered water in simulations.Biophysical journal · 2023Article
- The Advances and Limitations of the Determination and Applications of Water Structure in Molecular Engineering.International journal of molecular sciences · 2023Review
- Hydration and Structural Adaptations of the Human CYP1A1, CYP1A2, and CYP1B1 Active Sites by Molecular Dynamics Simulations.International journal of molecular sciences · 2023Article
- Screening and Biological Evaluation of Soluble Epoxide Hydrolase Inhibitors: Assessing the Role of Hydrophobicity in the Pharmacophore-Guided Search of Novel Hits.Journal of chemical information and modeling · 2023Article
- Water Networks Repopulate Protein-Ligand Interfaces with Temperature.Angewandte Chemie (International ed. in English) · 2022Article
- Deep learning-based molecular dynamics simulation for structure-based drug design against SARS-CoV-2.Computational and structural biotechnology journal · 2022Review
- From Data to Knowledge: Systematic Review of Tools for Automatic Analysis of Molecular Dynamics Output.Frontiers in pharmacology · 2022Review
- Structured Waters Mediate Small Molecule Binding to G-Quadruplex Nucleic Acids.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Biomolecular Simulations with the Three-Dimensional Reference Interaction Site Model with the Kovalenko-Hirata Closure Molecular Solvation Theory.International journal of molecular sciences · 2021Review
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Water plays a major role in ligand binding and is attracting increasing attention in structure-based drug design. Water molecules can make large contributions to binding affinity by bridging protein-ligand interactions or by being displaced upon complex formation, but these phenomena are challenging to model at the molecular level. Herein, networks of ordered water molecules in protein binding sites were analyzed by clustering of molecular dynamics (MD) simulation trajectories. Locations of ordered waters (hydration sites) were first identified from simulations of high resolution crystal structures of 13 protein-ligand complexes. The MD-derived hydration sites reproduced 73% of the binding site water molecules observed in the crystal structures. If the simulations were repeated without the cocrystallized ligands, a majority (58%) of the crystal waters in the binding sites were still predicted. In addition, comparison of the hydration sites obtained from simulations carried out in the absence of ligands to those identified for the complexes revealed that the networks of ordered water molecules were preserved to a large extent, suggesting that the locations of waters in a protein-ligand interface are mainly dictated by the protein. Analysis of >1000 crystal structures showed that hydration sites bridged protein-ligand interactions in complexes with different ligands, and those with high MD-derived occupancies were more likely to correspond to experimentally observed ordered water molecules. The results demonstrate that ordered water molecules relevant for modeling of protein-ligand complexes can be identified from MD simulations. Our findings could contribute to development of improved methods for structure-based virtual screening and lead optimization.
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