Sajadi Fatima, Rowley Christopher N
Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
PeerJ. 2018 Aug 14;6:e5472. doi: 10.7717/peerj.5472. eCollection 2018.
The CHARMM36 force field for lipids is widely used in simulations of lipid bilayers. The CHARMM family of force fields were developed for use with the mTIP3P water model. This water model has an anomalously high dielectric constant and low viscosity, which limits its accuracy in the calculation of quantities like permeability coefficients. The TIP3P-FB and TIP4P-FB water models are more accurate in terms of the dielectric constant and transport properties, which could allow more accurate simulations of systems containing water and lipids. To test whether the CHARMM36 lipid force field is compatible with the TIP3P-FB and TIP4P-FB water models, we have performed simulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers. The calculated headgroup area, compressibility, order parameters, and X-ray form factors are in good agreement with the experimental values, indicating that these improved water models can be used with the CHARMM36 lipid force field without modification when calculating membrane physical properties. The water permeability predicted by these models is significantly different; the mTIP3P-model diffusion in solution and at the lipid-water interface is anomalously fast due to the spuriously low viscosity of mTIP3P-model water, but the potential of mean force of permeation is higher for the TIP3P-FB and TIP4P-FB models due to their high excess chemical potentials. As a result, the rates of water permeation calculated the FB water models are slower than the experimental value by a factor of 15-17, while simulations with the mTIP3P model only underestimate the water permeability by a factor of 3.
用于脂质的CHARMM36力场在脂质双层模拟中被广泛使用。CHARMM系列力场是为与mTIP3P水模型一起使用而开发的。这个水模型具有异常高的介电常数和低粘度，这限制了其在诸如渗透系数等物理量计算中的准确性。TIP3P-FB和TIP4P-FB水模型在介电常数和传输性质方面更准确，这可以实现对包含水和脂质的系统进行更精确的模拟。为了测试CHARMM36脂质力场是否与TIP3P-FB和TIP4P-FB水模型兼容，我们对1,2-二棕榈酰-sn-甘油-3-磷酸胆碱和1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱双层进行了模拟。计算得到的头基面积、压缩性、序参数和X射线形状因子与实验值吻合良好，表明在计算膜物理性质时，这些改进的水模型可以直接与CHARMM36脂质力场一起使用而无需修改。这些模型预测的水渗透率有显著差异；由于mTIP3P模型水的粘度异常低，mTIP3P模型在溶液中和脂质-水界面的扩散异常快，但由于TIP3P-FB和TIP4P-FB模型的高过量化学势，它们的渗透平均力势更高。结果，使用FB水模型计算的水渗透速率比实验值慢15 - 17倍，而使用mTIP3P模型的模拟仅将水渗透率低估了3倍。
