Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related Cofactors from Quantum Mechanical Calculations.
Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related Cofactors from Quantum Mechanical Calculations.
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DOI：
10.1021/acs.jctc.7b01236
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发表时间：
2018-02-13
影响因子：
5.5
通讯作者：
Gumbart JC
中科院分区：
文献类型：
--
作者：
Pavlova A;Parks JM;Gumbart JC
钴胺素等类钴辅因子被许多酶所使用，对大多数生物体都是必不可少的。因此，有广泛的兴趣研究与分子动力学模拟钴胺蛋白相互作用。以前开发的钴胺素参数主要基于晶体结构数据。在这里，我们报告了从量子力学计算中得到的几种柱体的charmm兼容力场参数。我们提供了Co3+， Co2+和Co1+三种氧化态的corrinoids参数，以及不同的轴向配体。利用氦原子探针对Co（II）和Co(I)态钴中心的Lennard-Jones参数进行了优化，并结合自然居群分析（NPA）和抑制静电势（RESP）拟合方法获得了部分原子电荷。使用力场工具包对所有粘合项进行优化。结果参数仅由钴胺素单独或在水中的计算确定，然后通过评估它们与DFT几何形状的一致性，并通过分析几种可获得x射线晶体结构的类钴蛋白的分子动力学模拟轨迹来验证。在每个案例中，我们都获得了与参考数据非常一致的结果。与先前的charmm兼容钴胺素参数相比，我们观察到钴胺素结合位点的折叠角和较低的RMSD具有更好的一致性。本文描述的方法很容易适用于开发与charmm兼容的其他类柱体或大型生物分子的力场参数。
Corrinoid cofactors such as cobalamin are used by many enzymes and are essential for most living organisms. Therefore, there is broad interest in investigating cobalamin-protein interactions with molecular dynamics simulations. Previously developed parameters for cobalamins are based mainly on crystal structure data. Here, we report CHARMM-compatible force field parameters for several corrinoids developed from quantum mechanical calculations. We provide parameters for corrinoids in three oxidation states, Co3+, Co2+ and Co1+, and with various axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and Co(I) states were optimized using a helium atom probe, and partial atomic charges were obtained with a combination of natural population analysis (NPA) and restrained electrostatic potential (RESP) fitting approaches. The Force Field Toolkit was used to optimize all bonded terms. The resulting parameters, determined solely from calculations of cobalamin alone or in water, were then validated by assessing their agreement with DFT geometries and by analyzing molecular dynamics simulation trajectories of several corrinoid proteins for which X-ray crystal structures are available. In each case, we obtained excellent agreement with the reference data. In comparison to previous CHARMM-compatible parameters for cobalamin we observe a better agreement for the fold angle and lower RMSD in the cobalamin binding site. The approach described here is readily adaptable for developing CHARMM-compatible force-field parameters of other corrinoids or large biomolecules.
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影响因子：
15
作者：
HOOPS, SC;ANDERSON, KW;MERZ, KM
通讯作者：
MERZ, KM
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
5.5
作者：
Hart, Katarina;Foloppe, Nicolas;Baker, Christopher M.;Denning, Elizabeth J.;Nilsson, Lennart;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
7.8
作者：
Bridwell-Rabb J;Drennan CL
通讯作者：
Drennan CL
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD