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

Abstract

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.

Renjie Zhu

PhD Student in Chemistry

Hi, I am Renjie Zhu (朱 仁杰), a PhD student in Chemistry at Boston University. I received my Bachelor of Science degree in Chemistry from East China Normal University in 2025, where I spent four unforgettable and rewarding years. My given name shares the same Chinese characters as Di Renjie, a legendary detective figure. Therefore, I want to become a “detective” in the scientific world, using computational approaches to uncover the hidden mechanisms underlying chemical and biological systems.