The application of WaterMap-guided structure-based virtual screening in novel drug discovery

Kaczor, Agnieszka A.; Zięba, Agata; Matosiuk, Dariusz

doi:10.1080/17460441.2023.2267015

Cited by 3 publications

References 70 publications

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Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description

Menendez,

Accordino,

Loubet

et al. 2024

J. Phys. Chem. B

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V 4S , a new structural indicator for water specially designed to be suitable for hydration and nanoconfined contexts, has been recently introduced and preliminarily applied for water in contact with self-assembled monolayers and graphene-like systems. This index enabled an accurate detection of defective high local density water molecules (called HDA-like given their structural resemblance with the high-density amorphous ice, HDA). In the present work, we shall apply this new metric to characterize protein hydration water with particular interest in protein binding sites. As a first result, we shall find that protein hydration water has a higher concentration of HDA-like molecular arrangements compared to the bulk. Significantly, we shall show that the concentration of HDA-like molecules sharply decreases beyond the first hydration layer. Finally, we shall also reveal a highly nonuniform spatial distribution of the V 4S values for the first hydration shell on the protein surface, where the higher hydrophobicity inherent to the ligand binding site will be evident from an enrichment in HDA-like molecules as compared to the population exhibited by the global protein surface.

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Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description

Menendez,

Accordino,

Loubet

et al. 2024

J. Phys. Chem. B

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Perspectives on current approaches to virtual screening in drug discovery

Muegge,

Bentzien,

2024

Expert Opinion on Drug Discovery

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SuperWater: Predicting Water Molecule Positions on Protein Structures by Generative AI

Kuang,

Su,

Liu

et al. 2024

Preprint

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Water molecules play a significant role in maintaining protein structural stability and facilitating molecular interactions. Accurate prediction of water molecule positions around protein structures is essential for understanding their biological roles and has significant implications for protein engineering and drug discovery. Here, we introduce SuperWater, a novel generative AI framework that integrates a score-based diffusion model with equivariant graph neural networks to predict water molecule placements around proteins with high accuracy. SuperWater surpasses existing methods, delivering state-of-the-art performance in both crystal water coverage and prediction precision, achieving water localization within 0.3 ± 0.06 Å of experimentally validated positions. We demonstrate the capabilities of SuperWater through case studies involving protein hydration, protein-ligand binding, and protein-protein binding sites. This framework can be adapted for various applications, including structural biology, binding site prediction, multi-body docking, and water-mediated drug design.

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The application of WaterMap-guided structure-based virtual screening in novel drug discovery

Cited by 3 publications

References 70 publications

Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description

Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description

Perspectives on current approaches to virtual screening in drug discovery

SuperWater: Predicting Water Molecule Positions on Protein Structures by Generative AI

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The application of WaterMap-guided structure-based virtual screening in novel drug discovery

Cited by 3 publications

References 70 publications

Study of Protein Hydration Water with the V4S Structural Index: Focus on Binding Site Description

Study of Protein Hydration Water with the V4S Structural Index: Focus on Binding Site Description

Perspectives on current approaches to virtual screening in drug discovery

SuperWater: Predicting Water Molecule Positions on Protein Structures by Generative AI

Contact Info

Product

Resources

About

Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description

Study of Protein Hydration Water with the V_4S Structural Index: Focus on Binding Site Description