Conformation Dynamics of the Intrinsically Disordered Protein c-Myb with the ff99IDPs Force Field.
Conformation Dynamics of the Intrinsically Disordered Protein c-Myb with the ff99IDPs Force Field.
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作者：
Guo X;Han J;Luo R;Chen HF
本质上无序的蛋白质c-Myb在细胞增殖和分化中起关键作用。c-myb功能的缺失导致胚胎死亡，原因是胎儿肝造血功能的衰竭。本征无序的c-Myb的构象动力学仍然是未知的。在这里，分子动力学（MD）模拟与内在无序的蛋白质力场ff 99 IDPs被用来研究构象动力学。与ff 99 SBildn相比，ff 99 IDPs可以复制更多样化的c-Myb无序构象。在ff 99 IDPs下预测的二次化学位移比在ff 99 SBildn下更接近实验数据。因此，ff 99 IDP可以对c-Myb的天然熔融球、天然预熔融球和天然卷曲构象体进行采样。这些结果与其他内在无序蛋白的结果一致。动力学分析的MD模拟表明，c-Myb折叠通过一个两态的过程，并表明，c-Myb折叠的顺序三级折叠和螺旋折叠。KEL的折叠核在动态关联网络稳定折叠态中起着至关重要的作用。同时考察了TIP 3 P、TIP 4P-EW和TIP 5 P的溶剂模型的影响，发现TIP 3 P和ff 99 IDPs是研究c-Myb构象采样的最佳组合。这些结果揭示了c-Myb的构象动力学，并证实ff 99 IDPs力场可用于研究其他内在无序蛋白质的结构与功能关系。利用ff 99 IDPs力场研究了c-Myb的构象动力学。对天然熔融球、天然预熔融球和天然卷曲构象的代表性构象进行取样。
The intrinsically disordered protein c-Myb plays a critical role in cellular proliferation and differentiation. Loss of c-myb function results in embryonic lethality due to failure of fetal hepatic hematopoiesis. The conformation dynamics of the intrinsically disordered c-Myb are still unknown. Here, molecular dynamics (MD) simulations with the intrinsically disordered protein force field ff99IDPs were used to study the conformation dynamics. In comparison with ff99SBildn, ff99IDPs can reproduce more diverse disordered conformers of c-Myb. The predicted secondary chemical shift under ff99IDPs is more close to that of experiment data than that under ff99SBildn. Therefore, ff99IDPs can sample native molten globule, native pre-molten globule and native coil conformers for c-Myb. These results are consistent with those of other intrinsically disordered proteins. Kinetic analysis of MD simulations shows that c-Myb folds via a two-state process and indicates that c-Myb folds in the order of tertiary folding and helical folding. The folding nucleus of KEL plays an essential role in stabilizing the folding state with dynamic correlation networks. The influences of solvent models for TIP3P, TIP4P-EW and TIP5P were also investigated and it was found that TIP3P and ff99IDPs are the best combination to research the conformer sampling of c-Myb. These results reveal the conformation dynamics of c-Myb and confirm that the ff99IDPs force field can be used to research the relationship between structure and function of other intrinsically disordered proteins. The ff99IDPs force field was used to reveal the conformation dynamics of c-Myb. Representative conformers of native molten globule, native pre-molten globule and native coil conformers were sampled.