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Updated: May 15, 2026
09:42
Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Solvent fluctuations in hydrophobic cavity-ligand binding kinetics
Piotr Setny1, Riccardo Baron, Peter Michael Kekenes-Huskey
1Physics Department, Technical University Munich, D-85748 Garching, Germany.
Summary
Water dynamics significantly impact protein-ligand binding. Ligand approach amplifies pocket hydration fluctuations, increasing friction and slowing binding, highlighting hydrodynamic effects in molecular interactions.
Area of Science:
- Biophysics
- Computational Chemistry
- Molecular Dynamics
Background:
- Water is essential for protein-ligand binding.
- Understanding water's role in binding kinetics is crucial for drug discovery.
Purpose of the Study:
- Investigate water's role in ligand-protein binding kinetics.
- Analyze hydrodynamic effects and friction in a hydrophobic pocket.
Main Methods:
- Explicit-water molecular dynamics (MD) simulations.
- Implicit diffusional approaches.
- Analysis of diffusivity and friction profiles.
Main Results:
- Ligand approach amplifies pocket hydration oscillations.
- Increased friction near the pocket entrance decelerates binding.
- MD simulations show coupling between ligand motion and hydration fluctuations.
- Non-Markovian behavior observed in water-ligand forces.
Conclusions:
- Molecular-scale hydrodynamic effects are critical for cavity-ligand binding.
- Position-dependent friction profiles improve binding rate predictions.
- Spatiotemporal hydrodynamic coupling may facilitate induced-fit binding.
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