Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, USA.
J Phys Chem B. 2012 Aug 9;116(31):9424-31. doi: 10.1021/jp304056p. Epub 2012 Jul 3.
CHARMM36 (C36) is the most up-to-date pairwise additive all-atom lipid force field and is able to accurately represent bilayer properties of saturated and monounsaturated lipid molecules in the natural constant particle, pressure, and temperature (NPT) ensemble. However, molecular dynamics (MD) simulations on 1-stearoyl-2-docosahexaenoyl-sn-glycerco-3-phosphocholine (SDPC) bilayers of the polyunsaturated fatty acid (PUFA) chains result in inaccuracies of the surface area per lipid (SA), deuterium order parameters (S(CD)), and X-ray form factors. Therefore, in this study, high-level quantum mechanical calculations are used to improve the dihedral potential of neighboring double bonds, and the corresponding force field is referred to as C36p. The SA for SDPC at 303 K increases from 63.2 ± 0.2 (C36) to 70.8 ± 0.2 (C36p) Å(2) and agrees favorably with X-ray diffraction results at 297 K. The resulting S(CD) are in excellent agreement with experimental values of both the sn-1 and sn-2 chains. Calculated NMR (13)C relaxation times and X-ray form factors from MD simulations of SDPC bilayers also agree with experiments. MD simulations of 1,2-diarachidonyl-phosphatidylcholine (DAPC) bilayers are used to further validate our force field parameters on a lipid with both chains containing PUFAs. As expected, the thickness of DAPC bilayers is reduced, and the SA is increased compared to the SDPC bilayers. This update in the PUFA force field should allow for accurate MD simulations of PUFA-containing bilayers in the NPT ensemble.
CHARMM36（C36）是最新的成对加和全原子脂质力场，能够准确地表示在自然常粒子、压力和温度（NPT）系综中饱和和单不饱和脂质分子的双层性质。然而，在多不饱和脂肪酸（PUFA）链的 1-硬脂酰-2-二十二碳六烯酰-sn-甘油-3-磷酸胆碱（SDPC）双层上进行的分子动力学（MD）模拟会导致脂质表面积（SA）、氘序参数（S（CD））和 X 射线形态因子的不准确。因此，在本研究中，使用高级量子力学计算来改进相邻双键的二面角势，相应的力场称为 C36p。在 303 K 时，SDPC 的 SA 从 63.2 ± 0.2（C36）增加到 70.8 ± 0.2（C36p）Å2，与 297 K 的 X 射线衍射结果吻合良好。得到的 S（CD）与 sn-1 和 sn-2 链的实验值非常吻合。从 SDPC 双层的 MD 模拟计算的 NMR（13）C 弛豫时间和 X 射线形态因子也与实验结果一致。使用 1,2-二花生四烯酰基-磷酸胆碱（DAPC）双层的 MD 模拟进一步验证了我们在含有 PUFA 的脂质上的力场参数。正如预期的那样，与 SDPC 双层相比，DAPC 双层的厚度减小，SA 增大。这种在 PUFA 力场上的更新应该允许在 NPT 系综中对含有 PUFA 的双层进行准确的 MD 模拟。
