Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xin-Jie-Kou-Wai Street, Beijing 100875, China.
Phys Chem Chem Phys. 2023 Mar 1;25(9):6757-6767. doi: 10.1039/d2cp05384e.
Coarse-graining (CG) molecular dynamics (MD) simulations are widely used in interpreting experimental observations and predicting assembly morphology as well as collective behaviour but also face the problem of poor accuracy. A main issue is that cross-termed interactions between different CG beads are inadequately parameterized. This work proposes a novel top-down and bottom-up combined strategy to parameterize both self- and cross-termed interactions of zwitterionic phospholipids in water solution based on a piecewise Morse potential describing nonbonded van der Waals interactions. The self-interacting force parameters were optimized by matching experimental density, heat vapourization, and surface tension in a top-down manner, while the cross-termed interactions were optimized by fitting pseudo properties obtained from atomistic simulations in a bottom-up way, including mixing density, intermolecular energy, and radial mixing coefficient. The transferability of the CG force field (FF) was confirmed by reproducing a variety of structural and thermodynamic properties of lipid membranes in both liquid and gel phases. This FF can well depict vesicle self-assembly and vesicle fusion processes. Matching pseudo properties opens a new way to develop CG FF with increased accuracy and transferability.
粗粒化 (CG) 分子动力学 (MD) 模拟广泛应用于解释实验观测结果和预测组装形态以及集体行为，但也面临准确性差的问题。一个主要问题是不同 CG 珠粒之间的交叉项相互作用参数化不足。这项工作提出了一种新的自上而下和自下而上相结合的策略，基于描述非键范德华相互作用的分段 Morse 势，对水溶液中两性离子磷脂的自相互作用和交叉项相互作用进行参数化。通过自上而下的方式，根据实验密度、热蒸发和表面张力来优化自相互作用力参数，而通过自下而上的方式，根据从原子模拟中获得的伪性质（包括混合密度、分子间能量和径向混合系数）来优化交叉项相互作用。CG 力场 (FF) 的可转移性通过再现脂质膜在液相和凝胶相中的各种结构和热力学性质得到了证实。这个 FF 可以很好地描述囊泡的自组装和融合过程。匹配伪性质为开发具有更高准确性和可转移性的 CG FF 开辟了新途径。
