Getting the intermolecular forces correct: introducing the ASTA strategy for a water model.

Area of Science:

• Computational chemistry
• Molecular dynamics simulations
• Biophysics

Background:

• Accurate water force fields are crucial for simulating biological systems.
• Common three-site models (TIP3, SPC/ε, OPC3) offer decent bulk properties but lack realistic inter-atomic forces.
• Existing models are often parameterized using a top-down, experimental fitting approach.

Purpose of the Study:

• To test a bottom-up parameterization approach (ASTA) for water force fields.
• To investigate if optimizing inter-atomic forces improves geometrical and dynamical properties.
• To apply ASTA to both simple three-site and the polarizable AMOEBA force fields.

Main Methods:

• Developed and applied the Accurately System Tailored Atomic (ASTA) approach for force field parameterization.
• Optimized non-bonded inter-atomic forces directly, rather than fitting to bulk properties.
• Validated results against quantum chemical calculations for inter-molecular forces and experimental data for bulk properties (density, diffusion).

Main Results:

• The ASTA approach did not yield satisfactory results for simple three-site force fields with fixed charges.
• ASTA, with modifications, significantly improved the AMOEBA force field, yielding accurate intra- and inter-molecular forces.
• The modified ASTA approach accurately reproduced experimental water density and diffusion coefficients.

Conclusions:

• A bottom-up parameterization strategy focusing on inter-atomic forces can be highly effective, particularly for complex, polarizable force fields like AMOEBA.
• Optimizing fundamental inter-atomic interactions is key to achieving accurate molecular behavior and bulk properties.
• The ASTA approach offers a promising alternative for developing more realistic and predictive water models for molecular simulations.