调整高ATP度的ATP-ATP和ATP-失序蛋白相互作用,通过改变水模型
Toshifumi Mori1,2, Norio Yoshida3
1Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, Fukuoka 816-8580, Japan.
The Journal of chemical physics
|July 17, 2023
概括
选择正确的水模型显著影响了腺三酸盐 (ATP) 的分子动力学模拟及其与α-Synuclein等无序蛋白的相互作用,提高了聚合和结合研究的准确性.
科学领域:
- 生物物理学的生物物理.
- 计算生物学 计算生物学
- 分子动力学分子动力学
背景情况:
- 氨酸三酸盐 (ATP) 作为水基,影响蛋白质聚合物的溶解和液态-液态相分离.
- 分子动力学 (MD) 模拟对于研究ATP-蛋白相互作用至关重要,但与无序蛋白质和高ATP度面临挑战.
- 现有的水模型改善了无序的蛋白质描述,但它们对ATP相互作用的影响仍然未被探索.
研究的目的:
- 研究不同的水模型如何影响腺三酸盐 (ATP) 的行为及其与内在无序的蛋白质α-Synuclein的相互作用.
- 在分子动力学模拟中评估水模型对ATP-ATP和ATP-蛋白相互作用的影响.
主要方法:
- 使用三种不同的水模型进行分子动力学模拟:TIP4P-D,OPC和TIP3P.
- 保持蛋白质力场 (ff99SBildn) 恒定,以隔离水模型的影响.
- 分析了ATP聚合,ATP-ATP相互作用和ATP-蛋白与α-Synuclein结合的动态.
主要成果:
- TIP3P水模型导致了ATP的过度聚合,而TIP4P-D和OPC模型显示了单体和较小的集群.
- 在TIP3P中,ATP-蛋白相互作用过度稳定;TIP4P-D和OPC表现出动态的结合/解结合,与实验数据一致.
- 氨酸环相互作用显著调解了ATP-ATP和ATP-蛋白接触;用Na+替换Mg2+增强了静电相互作用,并促进了ATP的寡合化和结合.
结论:
- 水模型的选择极大地影响了腺三酸盐 (ATP) 特性及其与内在无序蛋白的相互作用的模拟精度.
- 与TIP4P-D和OPC水模型相比,TIP4P-D和OPC水模型提供了与TIP3P相比更现实的ATP行为和α-Synuclein相互作用描述.
- 水模型选择是一种有效的策略,可以提高缩ATP系统的分子动力学模拟的准确性.
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