Force field for molecular dynamics studies of glycine/water mixtures in crystal/solution environments

Abstract

Defining a force field for the theoretical predictions of the structure and growth of pharmaceutical crystals is very difficult because of the complex intermolecular bonding found in these crystals. Here, we investigate the accuracy of the AMBER ff03 force field for a-glycine molecules using molecular dynamics. The validation of the force field is carried out in both solution and crystal/solution environments. The molecule a-glycine is chosen because it has a simple molecular structure while displaying complex intermolecular interactions typical of pharmaceutical crystals. We estimate the atomic charge for glycine from density-functional theory and represent water by the extended simple point charge (SPC/E) model. In a pure solution environment, our simulation results agree well with the experimental data available for solution density, radial distribution functions, hydration number, and diffusion coefficient of glycine. In the crystal/solution environment, the lattice energy calculations are in agreement with the available literature results and also the force field is able to identify the hydrophilic nature of the (010) surface of glycine crystal. The good agreement between simulation results and experimental data indicates that the chosen force field can be used to investigate the growth of glycine crystals from aqueous solutions. © 2009 American Chemical Society.