Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.
Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.
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DOI：
10.1021/jp101759q
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发表时间：
2010-06-17
影响因子：
3.3
通讯作者：
Pastor, Richard W.
中科院分区：
文献类型：
--
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
对全原子加性CHARMM脂质力场（FF）进行了重大修改，并将其应用于含有胆碱和乙醇胺头部基团以及饱和和不饱和脂肪链的磷脂双层。由于当前的CHARMM脂质力场（C27和C27r）系统地得出的每个脂质的表面积值小于实验估计值，并且在远高于凝胶转变温度时双层呈现凝胶状结构，通过以量子力学（QM）和实验数据为目标，对选定的扭转、伦纳德 - 琼斯和部分原子电荷参数进行了修改。从对小分子的高水平从头算计算到对1,2 - 二棕榈酰 - sn - 磷脂酰胆碱（DPPC）双层的半经验量子力学研究，再结合实验热力学数据的量子力学计算被用作参数优化的目标数据。通过对以下六种脂质在高水合状态下的纯双层进行模拟来测试这些变化：DPPC、1,2 - 二肉豆蔻酰 - sn - 磷脂酰胆碱（DMPC）、1,2 - 二月桂酰 - sn - 磷脂酰胆碱（DLPC）、1 - 棕榈酰 - 2 - 油酰 - sn - 磷脂酰胆碱（POPC）、1,2 - 二油酰 - sn - 磷脂酰胆碱（DOPC）和1 - 棕榈酰 - 2 - 油酰 - sn - 磷脂酰乙醇胺（POPE）；还对低水合的DOPC双层进行了模拟。与实验表面积的一致性平均在2%以内，密度分布与中子和X射线衍射实验吻合良好。新力场能很好地预测核磁共振氘序参数（SCD），包括对DPPC、POPE和POPC双层中与羰基相邻的脂肪族碳的SCD的正确分裂。DPPC的面积压缩模量和13C核磁共振弛豫率的频率依赖性，以及低水合DOPC双层的水分布也与实验吻合良好。因此，所提出的脂质力场（称为C36）允许在无张力系综（NPT）中进行分子动力学模拟，并有望用于纯脂质系统以及包括膜蛋白在内的异质系统的模拟。
A significant modification to the additive all-atom CHARMM lipid force field (FF) is developed and applied to phospholipid bilayers with both choline and ethanolamine containing head groups and with both saturated and unsaturated aliphatic chains. Motivated by the current CHARMM lipid FF (C27 and C27r) systematically yielding values of the surface area per lipid that are smaller than experimental estimates and gel-like structures of bilayers well above the gel transition temperature, selected torsional, Lennard-Jones and partial atomic charge parameters were modified by targeting both quantum mechanical (QM) and experimental data. QM calculations ranging from high-level ab initio calculations on small molecules to semi-empirical QM studies on a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer in combination with experimental thermodynamic data were used as target data for parameter optimization. These changes were tested with simulations of pure bilayers at high hydration of the following six lipids: DPPC, 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1,2-dilauroyl-sn-phosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-phosphatidylethanolamine (POPE); simulations of a low hydration DOPC bilayer were also performed. Agreement with experimental surface area is on average within 2%, and the density profiles agree well with neutron and x-ray diffraction experiments. NMR deuterium order parameters (SCD) are well predicted with the new FF, including proper splitting of the SCD for the aliphatic carbon adjacent to the carbonyl for DPPC, POPE, and POPC bilayers. The area compressibility modulus and frequency dependence of 13C NMR relaxation rates of DPPC, and the water distribution of low hydration DOPC bilayers also agree well with experiment. Accordingly, the presented lipid FF, referred to as C36, allows for molecular dynamics simulations to be run in the tensionless ensemble (NPT), and is anticipated to be of utility for simulations of pure lipids systems as well as heterogeneous systems including membrane proteins.
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DOI：
10.1085/jgp.118.2.207
发表时间：
2001-08
期刊：
The Journal of general physiology
影响因子：
--
作者：
Crouzy S;Bernèche S;Roux B
通讯作者：
Roux B
影响因子：
3.7
作者：
Felleman, Daniel J.;Van Essen, David C.
通讯作者：
Van Essen, David C.
影响因子：
3.4
作者：
Benz, RW;Castro-Román, F;White, SH
通讯作者：
White, SH
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
5.5
作者：
Guvench, Olgun;Hatcher, Elizabeth;Venable, Richard M.;Pastor, Richard W.;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.