Development of CHARMM polarizable force field for nucleic acid bases based on the classical Drude oscillator model.
Development of CHARMM polarizable force field for nucleic acid bases based on the classical Drude oscillator model.
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DOI：
10.1021/jp1092338
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发表时间：
2011-01-27
影响因子：
3.3
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Baker, Christopher M.;Anisimov, Victor M.;MacKerell, Alexander D., Jr.
提出了一种基于经典德鲁德振子模型的核酸碱基极化力场。进行了参数优化，以再现晶体几何形状、晶体单位胞参数、升华热、振动频率和分配、偶极矩、分子极化率以及量子力学碱-碱和碱-水相互作用能。训练和验证数据包括未取代和烷基取代腺嘌呤、鸟嘌呤、胞嘧啶、尿嘧啶和胸腺嘧啶碱基晶体、水合晶体和氢键碱基对。在所有化合物中，计算的升华热的RMSD为4.1%。与非极化CHARMM27力场相比，这相当于精度提高了2.5 kcal/mol以上。然而，从非极化模型到极化模型，与实验分子体积的一致性从1.7%下降到2.1%。德鲁德极化力场显著改善了偶极矩的表示。与加性力场不同，不需要高估气相偶极矩，这说明了德鲁德极化力场能够准确地处理不同的介电环境，并表明了静电模型的改进。通过平均力势计算得到碱基对的气相结合焓，对模型进行了验证；加性模型和极化模型的平均差值分别为0.2和0.9 kcal/mol，均方根差值分别为1.3和1.7 kcal/mol。总的来说，考虑到与加性CHARMM力场相比的显著改进，将显式极化性纳入核酸碱基的力场代表了向生物系统精确计算建模迈出的又一步。
A polarizable force field for nucleic acid bases based on the classical Drude oscillator model is presented. Parameter optimization was performed to reproduce crystallographic geometries, crystal unit cell parameters, heats of sublimation, vibrational frequencies and assignments, dipole moments, molecular polarizabilities and quantum mechanical base-base and base-water interaction energies. The training and validation data included crystals of unsubstituted and alkyl-substituted adenine, guanine, cytosine, uracil, and thymine bases, hydrated crystals, and hydrogen bonded base pairs. Across all compounds, the RMSD in the calculated heats of sublimation is 4.1%. This equates to an improvement of more than 2.5 kcal/mol in accuracy compared to the non-polarizable CHARMM27 force field. However, the level of agreement with experimental molecular volume decreased from 1.7% to 2.1% upon moving from the non-polarizable to the polarizable model. The representation of dipole moments is significantly improved with the Drude polarizable force field. Unlike in additive force fields, there is no requirement for the gas-phase dipole moments to be overestimated, illustrating the ability of the Drude polarizable force field to treat accurately differently dielectric environments and indicating the improvements in the electrostatic model. Validation of the model was performed based on the calculation of the gas phase binding enthalpies of base pairs obtained via potential of mean force calculations; the additive and polarizable models both performed satisfactorily with average differences of 0.2 and 0.9 kcal/mol, respectively, and RMS differences of 1.3 and 1.7 kcal/mol, respectively. Overall, considering the number of significant improvements versus the additive CHARMM force field, the incorporation of explicit polarizability into the force field for nucleic acid bases represents an additional step toward accurate computational modeling of biological systems.
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影响因子：
4.4
作者：
Baucom, J;Transue, T;Sagui, C
通讯作者：
Sagui, C
DOI：
10.1107/s0108767301004810
发表时间：
2001-07-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION A
影响因子：
--
作者：
Apostolakis, J;Hofmann, DWM;Lengauer, T
通讯作者：
Lengauer, T
影响因子：
3.4
作者：
Deng, Nan-Jie;Cieplak, Piotr
通讯作者：
Cieplak, Piotr
影响因子：
1.7
作者：
BOYS, SF;BERNARDI, F
通讯作者：
BERNARDI, F
影响因子：
4.4
作者：
BEGLOV, D;ROUX, B
通讯作者：
ROUX, B