WaterMap is a computational tool used in drug discovery to analyze the thermodynamic properties of water molecules within and around biological macromolecules, such as proteins. It identifies water molecules that are energetically unfavorable (high energy) or favorable (low energy) in specific regions of the protein structure. High energy waters should be removed, or displaced by a ligand that makes similar interactions as the water molecule. By mapping these water molecules, WaterMap provides insights into how water contributes to the binding affinity and specificity of potential drug candidates.
Importance in Computational Drug Discovery
- Identification of Displacement Sites: WaterMap helps identify high-energy water molecules that can be potentially displaced by ligands, which could in theory increase binding affinity.
- Optimization of Binding Sites: It provides detailed information on the hydration thermodynamics of binding sites, aiding in the optimization of ligand binding.
- Prediction of Binding Affinity: By understanding the contribution of water molecules to the binding affinity, researchers can predict how modifications to a ligand could improve its interaction with the target protein.
- Design of Better Ligands: WaterMap enables the design of ligands that can displace high-energy water molecules or take advantage of low-energy waters (e.g. through water-mediated interactions), enhancing the potency and specificity of drug candidates.
- Understanding Protein Dynamics: It provides insights into the dynamic nature of water molecules around the protein, which is crucial for understanding protein-ligand interactions.
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