在整个Kemp消除酶变体中确定酶功能描述物的趋同
Yaoyukun Jiang1, Sebastian L Stull1, Qianzhen Shao1
1Department of Chemistry, Vanderbilt University, Nashville, TN 37235, United States of America.
Electronic structure (Bristol, England)
|July 10, 2023
概括
确定最佳的活性位区域大小对于使用分子模拟的酶工程至关重要. 这项研究发现了动态和静电描述器的特定距离切断值,以确保可靠的酶变体分析.
科学领域:
- 生物催化和酶工程 生物催化和酶工程
- 计算化学和分子建模.
- 蛋白质动力学和静电学
背景情况:
- 分子模拟通过提供酶功能描述器来加速生物催化发现.
- 这些描述符指导寻找有益的酶突变物.
- 对于跨酶变体的描述器计算的最佳活动位区域大小目前尚不清楚.
研究的目的:
- 测试动力学衍生和静电学描述符与不同规模的活跃站点区域的融合.
- 为了在酶工程中建立描述器计算的理想边界距离.
- 为选择适合预测建模的描述符提供参考.
主要方法:
- 对18种Kemp消除酶变体进行了融合试验,使用了6个活跃地点区域.
- 评估的描述因素包括活性位点的根平均平方偏差 (RMSD),溶剂可访问面积 (SASA) 比率和电场 (EF) 投影.
- 方法包括分子力学 (MM) 和量子力学/分子力学 (QM/MM).
主要成果:
- 蛋白质动力学描述器 (RMSD_active_site,SASA_ratio) 在离基质的5 Å切线处汇聚.
- 静电描述器 (EF_C-H) 在使用MM时汇聚在6 Å,在使用QM/MM时汇聚在4 Å.
- 斯皮尔曼相关性矩阵确定了描述器排名稳定的区域大小.
结论:
- 建立了用于可靠计算酶功能描述器的距离截止值.
- 提供了在计算酶工程中优化主动站点区域选择的关键见解.
- 旨在提高酶发现预测建模的准确性和效率.
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