Force field development for organic molecules: modifying dihedral and 1-n pair interaction parameters.

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Physical Chemistry

Background:

• Accurate molecular mechanics force fields (FFs) are crucial for molecular dynamics (MD) simulations.
• Existing FF parameterization methods may lack accuracy for certain molecular configurations, particularly hindered rotations.

Purpose of the Study:

• To develop and illustrate a general, systematic process for fitting all-atom molecular mechanics force field parameters.
• To enhance the accuracy of FF parameters for both intramolecular and intermolecular interactions.

Main Methods:

• Utilized quantum mechanical calculations and experimental thermodynamic data for parameter fitting.
• Introduced a 1-n scaling pair interaction format for strongly hindered intramolecular rotations.
• Systematically generated characteristic configurations to determine the optimal fitting order for FF parameters.
• Verified FF parameters self-consistently by comparing energies from FF and quantum mechanics for random molecular configurations from MD simulations.

Main Results:

• Successfully applied the systematic approach to obtain dihedral angle potential and 1-n scaling pair interaction parameters for 48 diverse organic molecules.
• Demonstrated the method's effectiveness using 3-hydroxypropionic acid as an example, comparing new parameters with existing ones.
• Showcased improved agreement between MD simulation results and experimental observations through adjusted intermolecular Van der Waals parameters.

Conclusions:

• The proposed systematic procedure provides a robust method for obtaining accurate dihedral and 1-n interaction potentials.
• This approach can be valuable for developing improved force fields, especially when parameters are unavailable in widely used existing FFs.
• The methodology offers a pathway to more reliable molecular dynamics simulations for a broader range of organic molecules.