Development of Shell-Space Electrostatic Potential Fitting Charges in a United-Atom Model for Amino Acids Simulations

Area of Science:

• Computational chemistry
• Biomolecular modeling
• Statistical mechanics

Background:

• Accurate electrostatic interactions are vital for coarse-grained (CG) models in biomolecular simulations.
• Existing methods for deriving partial charges in CG models may lack precision.
• All-atom (AA) models provide a high-fidelity reference for developing CG force fields.

Purpose of the Study:

• To develop a novel shell-space electrostatic potential (SS-ESP) method for deriving partial charges in CG models.
• To introduce a new Side-chain Reduced CG (SRCG) model for amino acids based on the SS-ESP method.
• To validate the accuracy of the SS-ESP method and the SRCG model against AA simulations.

Main Methods:

• Developed the shell-space electrostatic potential (SS-ESP) method to fit electrostatic potentials (ESPs) from AA models.
• Compared ESPs and electric dipole moments of CG charges derived from four different methods against AA amino acid models.
• Parametrized the SRCG force field using a bottom-up strategy: inherited bonding parameters from AA, derived CG charges via SS-ESP, and fitted Lennard-Jones parameters to van der Waals potentials.

Main Results:

• The SS-ESP method accurately reproduces ESPs and dipole moments compared to AA models.
• The SRCG model, parameterized using SS-ESP charges, shows consistency with AA simulations for dipeptides and tripeptides.
• The SRCG force field accurately predicts solvation free energies and maintains protein secondary structure stability.

Conclusions:

• The SS-ESP charge fitting method offers a robust framework for accurate electrostatic interactions in CG particles.
• The developed SRCG model provides a reliable and accurate representation of amino acids for protein simulations.
• This work advances the bottom-up development of protein CG models with improved electrostatic descriptions.