CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides.
CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides.
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DOI：
10.1021/acs.jcim.0c01360
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发表时间：
2021-02-22
影响因子：
5.6
通讯作者：
Im W
中科院分区：
文献类型：
--
作者：
Gao Y;Lee J;Smith IPS;Lee H;Kim S;Qi Y;Klauda JB;Widmalm G;Khalid S;Im W
氢质量再分配(HMR)通过增加氢原子的质量，允许全原子分子动力学模拟的时间步长高达4fs，已被用于蛋白质和磷脂双层分子模拟，以改进构象采样。通过CHARMM-图形用户界面生成的分子模拟输入现在支持各种模拟程序的HMR。此外，考虑到细菌外膜表面的模糊pH，在CHARMM-GUI型脂多糖模型器中还支持脂多糖中磷酸基团的不同质子化状态，无论是−2e还是−1e。为了考察HMR的稳健性以及磷酸盐基团的质子化状态对LPS双层性质的影响，用OpenMM 2-FS(标准)和4-FS(HMR)两种方案模拟了8个不同类型的具有两个磷酸盐质子化状态的LPS型全原子体系.通过标准模拟和HMR模拟得到的构象空间的一致性表明，即使在最复杂的生物分子之一的脂多糖中，HMR也是可靠的。对于具有不同质子化状态的体系，PO41−或PO42−基团的构象相似，但不同的磷质子化状态对脂类堆积和脂多糖酰链的构象性质影响不大。与含PO42−的体系相比，含PO41−的体系每种脂类的面积略小，因此脂质A酰链的有序性略高，这是因为即使在中和钙离子的情况下，PO42−之间的静电斥力也更大。CHARMM-图形用户界面中提供的HMR和不同质子化状态的脂多糖磷酸盐有望用于进一步研究不同来源的生物系统。
Hydrogen mass repartitioning (HMR) that permits time steps of all-atom molecular dynamics simulation up to 4 fs by increasing the mass of hydrogen atoms has been used in protein and phospholipid bilayers simulations to improve conformational sampling. Molecular simulation input generation via CHARMM-GUI now supports HMR for diverse simulation programs. In addition, considering ambiguous pH at the bacterial outer membrane surface, different protonation states, either −2e or −1e, of phosphate groups in lipopolysaccharides (LPS) are also supported in CHARMM-GUI LPS Modeler. To examine the robustness of HMR and the influence of protonation states of phosphate groups on LPS bilayer properties, eight different LPS-type all-atom systems with two phosphate protonation states are modeled and simulated utilizing both OpenMM 2-fs (standard) and 4-fs (HMR) schemes. Consistence in the conformational space sampled by standard and HMR simulations shows the reliability of HMR even in LPS, one of the most complex biomolecules. For systems with different protonation states, similar conformations are sampled with a PO41− or PO42− group, but different phosphate protonation states make slight impacts on lipid packing and conformational properties of LPS acyl chains. Systems with PO41− have slightly smaller area per lipid and thus slightly more ordered lipid A acyl chains compared to those with PO42−, due to more electrostatic repulsion between PO42− even with neutralizing Ca2+ ions. HMR and different protonation states of phosphates of LPS available in CHARMM-GUI are expected to be useful for further investigations of biological systems of diverse origin.
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影响因子：
3.3
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.
通讯作者：
Pastor, Richard W.
影响因子：
3.7
作者：
Jo S;Kim T;Im W
通讯作者：
Im W
影响因子：
3.4
作者：
Klauda, Jeffery B.;Roberts, Mary F.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
3.3
作者：
Klauda, Jeffery B.;Eldho, Nadukkudy V.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
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.