Refined OPLS All-Atom Force Field for Saturated Phosphatidylcholine Bilayers at Full Hydration

We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree–Fock (HF), (2) second order Møller–Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM).本研究报道了基于OPLS-AA全原子力场（Optimized Parameters for Liquid Simulations all-atom）框架下的二棕榈酰磷脂酰胆碱（dipalmitoyl-phosphatidylcholine, DPPC）参数化工作。本研究选择DPPC作为研究对象，原因在于其是研究最为广泛的磷脂类物质之一，拥有充足的实验数据可用于模型验证；同时它也是一类极具重要性且分布广泛的脂质，例如在肺表面活性剂中。此前尚未有针对磷脂酰胆碱（phosphatidylcholine, PCs）在OPLS-AA力场中的参数化研究，因此需要为该分子的极性与非极性部分分别推导成键与非键相互作用参数。本研究中，我们确定了磷脂酰胆碱、甘油结构单元以及酰基链中扭转角的相关参数，同时还计算了部分原子电荷。本次计算采用了三种方法：(1) 哈特利-福克方法（Hartree–Fock, HF），(2) 二级莫勒-普莱瑟微扰理论（second order Møller–Plesset perturbation theory, MP2），以及(3) 密度泛函理论（density functional theory, DFT）。我们还采用极化连续介质模型（polarizable continuum model, PCM）探究了极性环境的影响，并针对酰基链调整了范德华参数。最终共生成六组参数集，并在DPPC双分子层体系中开展测试。在这六组参数集中，仅有一组能够较为准确地复现脂质双分子层的实验数据。该成功的DPPC模型通过隐式极性环境（polarizable continuum model, PCM）下的MP2计算获得。