Non-bonded force field model with advanced restrained electrostatic potential charges (RESP2).

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Physical Chemistry

Background:

• The restrained electrostatic potential (RESP) method is standard for assigning molecular partial charges in simulations.
• RESP approximations in condensed-phase simulations lead to overpolarization and reduced accuracy.
• Accurate partial charges are crucial for reliable molecular simulations.

Purpose of the Study:

• To introduce RESP2, an advanced method for assigning partial charges.
• To improve the accuracy of partial charge calculations by tuning polarity.
• To optimize non-bonded force field parameters for enhanced simulation accuracy.

Main Methods:

• Development of the RESP2 approach, incorporating a parameter (δ) to scale gas- and aqueous-phase charge contributions.
• Optimization of the complete non-bonded force field, including Lennard-Jones parameters, against liquid properties.
• Validation of RESP2 using a reduced set of five Lennard-Jones types.

Main Results:

• RESP2 allows tuning of charge polarity by scaling quantum mechanical calculations.
• Optimizing the force field to liquid properties with RESP2 yields improved accuracy.
• A reduced set of five Lennard-Jones types is effective for force field optimization.

Conclusions:

• RESP2 with δ≈0.6 offers an accurate and robust method for generating partial charges.
• The method effectively balances gas- and aqueous-phase contributions for realistic molecular polarity.
• A minimal set of Lennard-Jones types provides a solid foundation for systematic force field re-optimization.