Water Migration through Enzyme Tunnels Is Sensitive to the Choice of Explicit Water Model

Area of Science:

• Biochemistry
• Computational Biology
• Molecular Dynamics

Background:

• Enzyme tunnels facilitate water transport, essential for substrate stabilization and product/inhibitor release.
• Water models in molecular dynamics simulations influence the accuracy of solvent and protein properties.

Purpose of the Study:

• To investigate the impact of different water models on water transport through enzyme tunnels.
• To determine if enzyme tunnel water transport is dependent on the selected water model.

Main Methods:

• Molecular dynamics simulations of enzymes with defined tunnel geometries.
• Systematic investigation using haloalkane dehalogenase, alditol oxidase, and cytochrome P450.
• Comparison of TIP3P, OPC, and TIP4P-Ew water models for water molecule transport analysis.

Main Results:

• TIP3P water models demonstrated significantly faster migration and higher water molecule transport compared to OPC and TIP4P-Ew.
• TIP4P-Ew showed more pronounced transport than OPC.
• Faster transit times of TIP3P water molecules through enzyme tunnels explained the increased migration.

Conclusions:

• Water model selection critically influences the simulation of water transport in enzyme tunnels.
• Accurate water models are crucial for simulating enzymatic reactions, enzyme design, and predicting drug interactions.