Interactions of Water and Alkanes: Modifying Additive Force Fields to Account for Polarization Effects

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Biomolecular modeling

Background:

• Atomistic simulations commonly use additive force fields (FF) with fixed point charges, neglecting molecular polarizability.
• This limitation leads to inaccuracies in modeling hydrophilic/hydrophobic interactions, notably overestimating water's transfer free energy to alkanes.

Purpose of the Study:

• To develop an efficient, automated workflow for optimizing pair-specific Lennard-Jones parameters in additive FFs.
• To improve the accuracy of biomolecular simulations by addressing the limitations of fixed-charge models.

Main Methods:

• An automated workflow was developed to optimize Lennard-Jones parameters within an additive FF framework.
• Water/hexadecane system was used as a prototype to target the free energy of water transfer.
• The optimized FF was applied to simulate five different lipid bilayers to assess water permeabilities.

Main Results:

• The optimized FF achieved quantitative agreement with experimental water transfer free energy to hexadecane and improved interfacial tension by 6%.
• Simulations showed significantly increased water permeabilities in lipid bilayers, correcting previous underestimations for both saturated and unsaturated bilayers.
• While some other properties showed decreased agreement, the method offers a parameter-specific route to improve diverse simulation observables.

Conclusions:

• Optimizing pair-specific Lennard-Jones parameters is an effective strategy to enhance the accuracy of additive force fields.
• This approach successfully improves the simulation of water-oil interfaces and membrane permeability, crucial for understanding biological systems.
• The developed workflow provides a flexible and efficient method for fine-tuning force fields for specific simulation targets.