Water at biomolecular binding interfaces

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Biophysics

Background:

• Water molecules at biomolecular interfaces mediate interactions via hydrogen bonds and van der Waals forces.
• Accounting for interfacial water is increasingly recognized as vital for accurate molecular docking and binding affinity predictions.

Purpose of the Study:

• To review experimental and theoretical studies on the influence of interfacial water on binding thermodynamics.
• To highlight recent findings using inhomogeneous fluid solvation theory and predict thermodynamic consequences of water displacement.

Main Methods:

• Review of existing experimental and theoretical literature.
• Application of inhomogeneous fluid solvation theory.
• Analysis of thermodynamic consequences of displacing bound water molecules.

Main Results:

• Interfacial water plays a critical role in the thermodynamics of biomolecular complex formation.
• Inhomogeneous fluid solvation theory provides a framework for quantifying water's influence.
• Ligand modification can alter the thermodynamic impact of bound water displacement.

Conclusions:

• Quantifying the thermodynamic contribution of interfacial water is essential for understanding biomolecular recognition.
• Further theoretical and experimental advancements are needed to fully elucidate the role of water in binding.
• This knowledge can guide the design of novel therapeutics with improved binding characteristics.