Recent progress in general force fields of small molecules.

Area of Science:

• Computational chemistry
• Molecular modeling
• Drug discovery

Background:

• Recent progress in computational hardware and free energy algorithms facilitates molecular simulations.
• Molecular mechanics force fields (FFs) for small molecules have significantly improved in accuracy, usability, and speed between 2018-2020.

Purpose of the Study:

• To highlight recent advancements in molecular simulation techniques for receptor-ligand binding.
• To discuss improvements in molecular mechanics force fields, including chemical space coverage, charge models, and parameterization.

Main Methods:

• Utilizing advanced computational hardware and free energy algorithms for molecular simulations.
• Applying updated molecular mechanics force fields with enhanced accuracy and user-friendliness.
• Incorporating new charge models and chemical perception methods.
• Leveraging automated parameterization toolkits, including machine learning.

Main Results:

• Expanded chemical space coverage for ligand-like molecules in popular classical additive and polarizable FFs.
• Introduction of novel charge models for improved accuracy and transferability.
• Implementation of advanced chemical perception to move beyond predefined atom types.
• Development of automated parameterization toolkits for enhanced user convenience.

Conclusions:

• Modern molecular simulation and force field developments enable more robust and efficient analysis of molecular interactions.
• These advancements support broader applications in drug discovery and materials science.
• Improved FFs and user-friendly tools accelerate the molecular modeling workflow.