(367e) Application of Kirkwood-Buff Integral Data in Development of a Charmm-Type Carbohydrate Force Field to Model Activity Behavior

Kirkwood-Buff theory relates radial distribution functions of molecules in binary solutions to thermodynamic properties, including partial molar volumes, isothermal compressibilities, and activity coefficient derivatives. Because radial distribution functions can be easily obtained from molecular dynamics simulations, this allows for the connection of simulation results to experiment.

The experimental data used in the development of force field parameters can significantly impact the quality of the resulting model. For carbohydrates, the experimental data included in force field development often includes data on pure carbohydrate behavior, including heats of vaporization and crystal structure parameters. We found that the current CHARMM force field did not reproduce the experimental activity behavior of lower-concentration aqueous carbohydrate solutions, both in binary carbohydrate-water systems and in ternary protein-carbohydrate-water systems, and speculated that this was a result of the parameterization method.

We applied Kirkwood-Buff theory in the development of new alcohol force field parameters, and we will describe these parameters and their validation on glycerol, sorbitol, glucose, sucrose, and trehalose. The resulting force field parameters better match experimental Kirkwood-Buff data on carbohydrate-carbohydrate, carbohydrate-water, and water-water interactions as compared to current CHARMM parameters, and in particular better match the trends in activity coefficient derivative behavior. Additionally, we will demonstrate these parameters can be used to model experimental protein-carbohydrate-water interactions.