Restrained electrostatic potential atomic partial charges for condensed-phase simulations of carbohydrates

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Biomolecular Modeling

Background:

• Electrostatic Potential (ESP) charges are crucial for macromolecular simulations but often overestimate interaction strengths.
• RESP-charges offer an attenuated alternative, with existing parameters for proteins and nucleic acids.
• Accurate partial atomic charges are essential for modeling carbohydrate and glycoprotein crystal structures.

Purpose of the Study:

• To develop and validate a novel method for determining RESP-charges specifically for carbohydrates.
• To assess the suitability of different charge sets for carbohydrate simulations using molecular dynamics.
• To optimize parameters for the GLYCAM force field in carbohydrate simulations.

Main Methods:

• Utilized molecular dynamics (MD) simulations of carbohydrate crystal structures.
• Employed a restraint function during the fitting of partial charges to electrostatic potentials.
• Monitored crystallographic unit cell geometry as a sensitivity indicator for partial charges.
• Evaluated charge sets using neutron diffraction data for α-d-glucopyranose.

Main Results:

• A restraint weight of 0.01 yielded the best agreement between simulated and neutron diffraction structures of α-d-glucopyranose.
• Unrestrained ESP-charges and charges from Mulliken/distributed multipole analyses showed poor performance.
• The proposed MD-based approach effectively assesses partial charge suitability for carbohydrates.

Conclusions:

• The novel MD simulation approach provides a reliable method for determining RESP-charges for carbohydrates.
• Optimized RESP-charges are critical for accurately reproducing carbohydrate crystal geometries in simulations.
• This work enhances the accuracy of carbohydrate and glycoprotein simulations within the GLYCAM framework.