过渡状态振动分析和COMT催化甲基转移的同位素效应
1Departament de Química Física i Analítica, Universitat Jaume I, 12071 Castellón, Spain.
Journal of the American Chemical Society
|August 20, 2020
概括
这项研究分析了甲基转移反应的同位素分离函数比率 (IPFR),发现较小的计算模型可以准确预测 IPFR,但不能预测碳-14 IPFR. 权重影响影响IPFR,蛋白质对过渡载体的贡献是最小的.
科学领域:
- 计算化学
- 酶催化
- 生物物理化学
背景情况:
- 甲基转移酶 (COMT) 催化甲基转移反应.
- 同位素分离函数比 (IPFR) 对于理解反应机制和同位素效应至关重要.
- 混合量子力学/分子力学 (QM/MM) 方法用于模拟复杂的酶系统.
研究的目的:
- 在COMT催化甲基转移中分析过渡结构的IPFR.
- 批判性地评估较小的计算模型 (Hessian) 复制IPFR趋势的能力.
- 调查积效应和蛋白质残留对IPFR的影响.
主要方法:
- 使用混合QM/MM方法计算TS的IPFR.
- 对较小的提取的Hessian与较大的QM/MM Hessian进行IPFR准确性的分析.
- 计算频率,平均平方幅度和潜在能量扫描以评估性.
- 通过改变系统质量来研究权衡效应.
主要成果:
- 一个精确复制的6原子 (α-T3) IPFR,但不是α-碳-14 (α-14C) IPFR.
- 沉重效应显示,随着系统质量的增加,α-14C IPFR趋向最小,α-T3 IPFR趋向最大.
- 过渡载体主要由甲基供体和接受体内的运动组成,蛋白质残留的贡献最小.
- 价值力常数与之前的估计有很大的不同,挑战了压缩假设.
结论:
- 较小的计算模型不足以准确预测COMT催化中的所有同位素效应.
- 沉重效应在IPFR的确定中起着重要作用,特别是在较重的同位素中.
- 催化机制似乎没有受到蛋白质残留相互作用或压缩效应的强烈影响.
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