Docking data of selected human linker histone variants to the nucleosome.

Different human linker histone (H1) variants are expected to have distinct binding modes to the nucleosome.
The position and orientation of a number of different H1 globular domains on the nucleosome were investigated through molecular docking using MGLTools and HADDOCK. The nucleosome core and linker DNA in the GH5-chromatosome structure (PDB: 4QLC) were used as a docking template. GH5 (in PDB: 4QLC) was re-docked to this template to test the docking algorithm.

Docked and re-docked GH5 compared well. The docking algorithm was further tested by docking the NMR solution structure of the globular domain of chicken H1 (GH1, PDB: 1GHC) to the nucleosome template. The position of docked GH1 on the nucleosome agreed with literature.


The N-terminal - and globular domain H1x hybrid (NGH1x) was studied using solution NMR in both low (20 mM sodium phosphate, pH 7.0) and high (20 mM sodium phosphate, 1 M sodium perchlorate, pH 7.0) ionic strength conditions (de Wit, H., Vallet, A., Brutscher, B. et al. Biomol NMR Assign (2019) 13: 249. https://doi.org/10.1007/s12104-019-09886-x). These low and high ionic strength structures were docked to the nucleosome template.


Homology (MODELLER) and ab initio modeling (CS-ROSETTA) were employed to model structures for other human H1 globular domains: GH1.0, GH1.4, GH1oo, and GH1t. The modeled structures were also docked to the nucleosome template.


All the docking procedures listed above produced 100 models of different energies. In each case, the lowest energy docked model was chosen. The structures of all the H1 globular domains that were docked to the template are given as PDB files (1GHC_lowest_energy.pdb; 2LSO_lowest_energy.pdb; GH5_re-docked_position.pdb; NGH1x_high_salt_NTD.pdb; NGH1x_low_salt_NTD.pdb; modeled_GH1_0_lowest_energy.pdb; modeled_GH1_4_lowest_energy.pdb; modeled_GH1oo_lowest_energy.pdb; modelled_GH1t_lowest_energy.pdb) in the data file. The nucleosome template structure is also given in PDB file format (4QLC_nucleosome_without_GH5.pdb). Finally, the docked models are also given (GH5-chromatosome.pdb; 1GHC-chromatosome.pdb; 2LSO-chromatosome.pdb; GH1_0-chromatosome.pdb; GH1_4-chromatosome.pdb; GH1oo-chromatosome.pdb; GH1t-chromatosome.pdb; NGH1x_no_salt-chromatosome.pdb; NGH1x_salt-chromatosome.pdb). The files are compatible with most molecular graphics software.

The file Dockings_modelling_test_and_results.pdf provides the modeling and docking results in figures and tables. A short description of each figure and table is given within the PDF file.

不同的人类连接组蛋白H1（linker histone H1）变体与核小体（nucleosome）的结合模式理应存在差异。研究人员借助MGLTools与HADDOCK工具开展分子对接（molecular docking）实验，探究了多种不同的H1球状结构域在核小体上的定位与取向。本次分子对接的模板采用了GH5-染色质小体结构（PDB: 4QLC）中的核小体核心与连接DNA序列。首先将PDB条目4QLC中的GH5重新对接至该模板，以验证对接算法的有效性。

重新对接得到的GH5结构表现良好，随后研究人员又将鸡H1球状结构域的核磁共振（NMR）溶液结构（GH1，PDB: 1GHC）对接至核小体模板，以此进一步测试对接算法。对接得到的GH1在核小体上的定位与已有文献报道结果一致。

研究人员还在低离子强度（20 mM 磷酸钠，pH 7.0）与高离子强度（20 mM 磷酸钠，1 M 高氯酸钠，pH 7.0）两种条件下，通过溶液核磁共振技术对N端与球状结构域融合的H1x变体（NGH1x）开展了研究（de Wit, H., Vallet, A., Brutscher, B. et al. Biomol NMR Assign (2019) 13: 249. https://doi.org/10.1007/s12104-019-09886-x）。随后将这两种离子强度条件下得到的NGH1x结构对接至核小体模板。

研究人员还采用同源建模（MODELLER）与从头建模（ab initio modeling，CS-ROSETTA）技术，对其余人类H1球状结构域（GH1.0、GH1.4、GH1oo与GH1t）的结构进行了建模，并将所建模型同样对接至核小体模板。

上述所有对接流程均生成了100个不同能量等级的模型，最终选取每个案例中能量最低的对接模型。所有用于对接的H1球状结构域的结构均以PDB格式文件提供（1GHC_lowest_energy.pdb；2LSO_lowest_energy.pdb；GH5_re-docked_position.pdb；NGH1x_high_salt_NTD.pdb；NGH1x_low_salt_NTD.pdb；modeled_GH1_0_lowest_energy.pdb；modeled_GH1_4_lowest_energy.pdb；modeled_GH1oo_lowest_energy.pdb；modelled_GH1t_lowest_energy.pdb），数据文件中同时提供了核小体模板结构的PDB格式文件（4QLC_nucleosome_without_GH5.pdb）。此外，最终的对接模型也一并提供：GH5-chromatosome.pdb；1GHC-chromatosome.pdb；2LSO-chromatosome.pdb；GH1_0-chromatosome.pdb；GH1_4-chromatosome.pdb；GH1oo-chromatosome.pdb；GH1t-chromatosome.pdb；NGH1x_no_salt-chromatosome.pdb；NGH1x_salt-chromatosome.pdb。这些文件兼容绝大多数分子可视化软件。

文件Dockings_modelling_test_and_results.pdf以图表形式呈现了建模与对接的结果，PDF文件内部还附带了每张图表与表格的简要说明。