Polarizable Multipole-Based Force Field for Dimethyl and Trimethyl Phosphate

Area of Science:

• Computational chemistry
• Biomolecular modeling
• Force field development

Background:

• Phosphate groups in biomolecules present modeling challenges due to their charge and polarizability.
• Classical force fields struggle to accurately represent phosphate compounds.
• Accurate modeling is crucial for understanding biomolecular function.

Purpose of the Study:

• Develop and validate the AMOEBA force field for dimethyl phosphate (DMP) and trimethyl phosphate (TMP).
• Improve the simulation accuracy of phosphate-containing biomolecules.
• Investigate the impact of the environment on molecular conformation and energy.

Main Methods:

• Quantum mechanical (QM) studies, including ab initio calculations (MP2/cc-pVQZ).
• Development of a many-body polarization model using Thole-style induction.
• Parameterization of van der Waals interactions and introduction of stretch-torsion coupling terms.
• Liquid-phase simulations and condensed-phase validation for TMP.

Main Results:

• The developed AMOEBA force field accurately describes DMP and TMP molecular structure and conformational energy landscapes.
• It captures bond and angle variations with conformation and interactions with water and metal ions.
• Condensed-phase simulations for TMP show good agreement with experimental properties like hydration free energy and liquid density.
• Significant differences in polarization behavior were observed between liquid TMP and TMP in water.

Conclusions:

• The AMOEBA force field provides a significant advancement for modeling phosphate-containing biomolecules.
• Accurate representation of polarization and environmental effects is critical for biomolecular simulations.
• This work enables more reliable computational studies of nucleic acids, lipids, and related compounds.