在阿扎酸中的氨酸残留物对构造空间的邻居作用
Ho-Jin Lee1,2, Shi-Wei Liu3, Máté Sulyok-Eiler4,5
1Division of Natural and Mathematics Sciences, LeMoyne-Own College, Memphis, TN, 38126, USA.
Heliyon
|July 18, 2024
概括
邻居效应和溶剂显著影响亚酸中的氨酸残留结构,影响蛋白质折叠研究. 这些发现对于开发精确的的计算力场至关重要.
科学领域:
- 计算化学和分子建模.
- 生物物理化学和蛋白质科学 生物物理化学和蛋白质科学
背景情况:
- 对于蛋白质折叠研究和准确的计算力场的开发,了解氨酸 (Ala) 残留的构造性质至关重要.
- 邻近的残留物效应和溶剂相互作用在确定的结构和动态方面发挥着重要作用.
研究的目的:
- 调查邻近的azaGly残留物对模拟阿扎酸中的Ala残留物的构造景观的影响.
- 评估溶解模型对阿拉残留物预测的形状偏好的影响.
- 通过实验合成和阿扎的结构分析来验证理论预测.
主要方法:
- 通过使用DFT函数 (LCgau-BOP和LCgau-BOP + LRD) 来生成Ramachandran能量地图,用于模型阿扎 (Ac-Ala-azaGly-NHMe和Ac-azaGly-Ala-NHMe) 中的Ala残留.
- 应用溶解模型,包括IEF-PCM和SMD,以模拟气体和水相条件.
- 合成和X射线晶体分析阿扎酸Ac-azaGly-Ala-NH2 (aGA2) 以实验性确定形状偏好.
主要成果:
- 邻近的azaGly残留物的构造决定了在隔离的阿扎型模型中Ala残留物的首选构造.
- 在水性环境中,Ala残留物有利于聚二烯 (βP),三角形右螺旋 (δR) 和右螺旋 (αR) 形状,无论其位置如何.
- 阿扎酸aGA2的X射线结构证实了理论预测,在βP中显示了azaGly,在αR结构中显示了Ala;SMD/LCgau-BOP + LRD方法与实验数据有很好的一致性.
结论:
- 邻近的残留物效应和溶剂相互作用是模型阿扎酸中Ala残留物的结构偏好的关键决定因素.
- 选择的DFT函数和溶解模型 (SMD/LCgau-BOP + LRD) 提供了可靠的预测.
- 这些发现有助于更好地理解的结构-性质关系,并改进生物分子的计算模型.
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