Enhancing the Simulation Accuracy of Small Organic Molecules with an Optimized Lennard-Jones Coarse-Grained Model

Developing accurate coarse-grained (CG) molecular models is crucial for building databases of complex chemical molecules and conducting related data-driven research. The accuracy of CG models is typically affected by CG bead resolution and non-bonded interaction parameters. In this study, an optimized Lennard-Jones (LJ) CG model (OLJCG) for small organic molecules was developed with parameters derived from the general Amber force field. The performance of the OLJCG model was evaluated by simulating the density of organic molecules, vaporization enthalpy, non-aqueous solvation free energy, and hydration free energy. CG molecular dynamics (CGMD) simulations demonstrate that introducing optimized LJ parameters into the OLJCG model effectively enhances the description of non-bonded interactions between CG particles. The optimization strategy proposed in this paper provides an accurate and systematic method for future development of CG small molecule databases.