A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat
A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat
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DOI：
10.1080/07391102.1999.10508297
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发表时间：
1999-02-01
影响因子：
4.4
通讯作者：
Kollman, PA
中科院分区：
文献类型：
--
作者：
Cheatham, TE;Cieplak, P;Kollman, PA
我们已经研究了对康奈尔等人的力场进行的一些细微的参数修改。该力场在重现核酸特性方面已被证明是相当成功的，但其对B - DNA的C2'-内式糖环折叠相位和螺旋重复似乎有所低估。令人鼓舞的是，添加一个涉及原子C(sp(3)) - O - (sp(3)) - C(sp(3)) - N(sp(2))的单一V(2)项，由于异头效应（氧上的孤对电子相对于吸电子的N优先取向），该项可以很好地被合理化，这使得C2'-内式糖的糖环折叠相位与从头算计算结果近乎完美一致（W接近162度）。其次，对整个核苷进行高水平的从头算计算（与1994 - 1995年因计算机限制而必须使用的较小模型系统形成对比），可以改进核酸的χ扭转势能。最后，对O(sp(3)) - C(sp(3)) - C(sp(3)) - O(sp(3))的V(2)扭转势能进行了经验性调整，以重现从头算计算得到的C2'-内式和C3'-内式核苷的相对能量。这些修改在单核苷的分子动力学模拟（以评估糖环折叠百分比）以及DNA和RNA的双螺旋（以评估螺旋和序列特异性结构特性）中进行了测试。在这两个方面，修改后的力场都提高了与实验数据的一致性。
We have examined some subtle parameter modifications to the Cornell et al. force field, which has proven quite successful in reproducing nucleic acid properties, but whose C2'-endo sugar pucker phase and helical repeat for B DNA appear to be somewhat underestimated. Encouragingly, the addition of a single V(2) term involving the atoms C(sp(3))-O-(sp(3))-C(sp(3))-N(sp(2)), which can be nicely rationalized because of the anomeric effect (lone pairs on oxygen are preferentially oriented relative to the electron withdrawing N), brings the sugar pucker phase of C2'-endo sugars to near perfect agreement with ab initio calculations (W near 162 degrees). Secondly, the use of high level ab initio calculations on entire nucleosides (in contrast to smaller model systems necessitated in 1994-95 by computer limitations) lets one improve the chi torsional potential for nucleic acids. Finally, the O(sp(3))-C(sp(3))-C(sp(3))-O(sp(3)) V(2) torsional potential has been empirically adjusted to reproduce the ab initio calculated relative energy of C2'-endo and C3'-endo nucleosides. These modifications are tested in molecular dynamics simulations of mononucleosides (to assess sugar pucker percentages) and double helices of DNA and RNA (to assess helical and sequence specific structural properties). In both areas, the modified force field leads to improved agreement with experimental data.