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适应的DFTB3排斥潜力达到DFT精度,用于酶中的化物转移反应

José Luís Velázquez-Libera^1,2, Rodrigo Recabarren³, David Adrian Saez⁴

¹Departamento de Química Física, Universitat de Valencia, Valencia, Spain.

Journal of computational chemistry

|July 14, 2025

概括

这项研究增强了DFTB3方法,用于建模酶化物转移反应. 改进的方法准确地预测激活障碍,使酶工程和药物设计的高效计算模拟成为可能.

科学领域:

生物化学生物化学
计算化学计算化学
酶学是一种酶学.

背景情况:

酶体化物转移反应在新陈代谢中至关重要,但在计算上很难准确地建模.
像DFT QM/MM这样的当前方法提供了准确性,但在计算上昂贵,限制了大规模的模拟.
像DFTB3这样的半经验方法提供了效率,但对这些反应缺乏准确性.

研究的目的:

提高DFTB3方法的准确性,用于建模酶体化物转移反应.
开发一种系统的方法来优化DFTB3对反应潜能表面的描述.
为了实现更高效,更准确的酶机制的计算模拟.

主要方法:

修改了DFTB3排斥潜能函数,使用对函数的线性组合.
基于反应路径上的C-H和C-C距离分布的引导优化.
验证了适应的DFTB3汉密尔顿对Crotonyl-CoA碳氧化酶/降解酶 (Ccr),1,4-二二氨酸反应和二叶酸降解酶 (DHFR) 的反应.

主要成果:

优化的DFTB3哈密尔顿准确地复制了Ccr (在0.1kcal/mol内) 的参考DFT激活屏障.
适应的方法成功预测了其他化物转移反应 (1,4-二二和DHFR) 的激活障碍,匹配了DFT和实验数据.
在描述化物转移的潜在能量表面方面取得了重大改进.

结论:

开发的DFTB3修改为建模酶体化物转移反应提供了一种计算效率高,准确的方法.
这种方法可以进行更广泛的分子动力学模拟,有助于酶工程和药物发现.
优化汉密尔顿的跨不同酶系统的可转移性证明了它的广泛适用性.

关键词:

这是DFTB3DFTB3 QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM QM/MM 适应性串式方法适应性串式方法和的功能是和的功能.它们具有排斥性的潜力.重新参数化的重新参数化

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