突变对神经毒性降低的新化学基因 reteplase 的影响,这是一个计算研究
Pardis Mohammadi Pour1, Karim Mahnam2, Mahsa Taherzadeh3
1Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Research in pharmaceutical sciences
|August 24, 2023
概括
新的 reteplase 变体显示与N-甲基-d-亚斯巴达酸谷氨酸受体 (NMDAR) 的相互作用减少,可能降低神经毒性. 这一发现可能会导致急性缺血性中风的更安全的治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 兴奋毒性是一种神经毒性,涉及过度刺激N-甲基-d-阿斯巴酸酸盐受体 (NMDAR),导致细胞死亡.
- 像reteplase这样的等离子原激活剂可以通过与NMDAR NR1子单元的氨基末端域 (ATD) 的相互作用引起兴奋毒性.
研究的目的:
- 通过计算评估野生类型 reteplase 和 NMDAR ATD.之间的相互作用.
- 评估两种新奇的仿真网置酶变体的相互作用,在 kringle2 域中发生突变,与 NMDAR ATD.
主要方法:
- 同性学建模的模拟.
- 蛋白质对接是指蛋白质对接.
- 分子动态模拟分子动态模拟
- 分子动力学轨迹分析分析
主要成果:
- 自由能量分析显示,与野生类型的 reteplase 相比,仿真 reteplase 变体 (M1-chr,M2-chr) 和 NMDAR ATD 之间的相互作用明显较低.
- 野生类型的 reteplase: -2127.516 ± 0.0; M1-chr: -1761.510 ± 0.0; M2-chr: -521.908 ± 0.0.0 在这种情况下,我们可以使用
结论:
- 与NMDAR ATD相结合的奇美基网置酶变异的减少相互作用表明与之相关的神经毒性较低.
- 这些变异可能代表急性缺血性中风治疗的潜在治疗候选者,需要进一步调查.
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