Rapid Convergence of Energy and Free Energy Profiles with Quantum Mechanical Size in Quantum Mechanical–Molecular Mechanical Simulations of Proton Transfer in DNA,Journal of Chemical Theory and Computation

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Rapid Convergence of Energy and Free Energy Profiles with Quantum Mechanical Size in Quantum Mechanical–Molecular Mechanical Simulations of Proton Transfer in DNA
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2018-02-15 00:00:00 , DOI: 10.1021/acs.jctc.7b00964
Susanta Das ₁ , Kwangho Nam _{2,

3} , Dan Thomas Major ₁

Affiliation

In recent years, a number of quantum mechanical–molecular mechanical (QM/MM) enzyme studies have investigated the dependence of reaction energetics on the size of the QM region using energy and free energy calculations. In this study, we revisit the question of QM region size dependence in QM/MM simulations within the context of energy and free energy calculations using a proton transfer in a DNA base pair as a test case. In the simulations, the QM region was treated with a dispersion-corrected AM1/d-PhoT Hamiltonian, which was developed to accurately describe phosphoryl and proton transfer reactions, in conjunction with an electrostatic embedding scheme using the particle-mesh Ewald summation method. With this rigorous QM/MM potential, we performed rather extensive QM/MM sampling, and found that the free energy reaction profiles converge rapidly with respect to the QM region size within ca. ±1 kcal/mol. This finding suggests that the strategy of QM/MM simulations with reasonably sized and selected QM regions, which has been employed for over four decades, is a valid approach for modeling complex biomolecular systems. We point to possible causes for the sensitivity of the energy and free energy calculations to the size of the QM region, and potential implications.

中文翻译：

DNA质子转移的量子力学-分子力学模拟中能量和自由能分布随量子力学尺寸的快速收敛

近年来，许多量子机械-分子机械（QM / MM）酶研究已经通过能量和自由能计算研究了反应能对QM区域大小的依赖性。在这项研究中，我们使用DNA碱基对中的质子转移作为测试案例，在能量和自由能计算的背景下，重新讨论了QM / MM模拟中QM区域大小依赖性的问题。在模拟中，对QM区域进行了色散校正的AM1 / d-PhoT哈密顿量处理，该方法被开发为可准确描述磷酰基和质子转移反应，并结合了使用粒子网状Ewald求和方法的静电嵌入方案。凭借如此严格的QM / MM潜力，我们进行了相当广泛的QM / MM采样，并发现，自由能反应曲线相对于QM范围内的QM区域迅速收敛。±1大卡/摩尔这一发现表明，采用合理大小和选定的QM区域进行QM / MM模拟的策略已经使用了40多年，它是对复杂的生物分子系统进行建模的有效方法。我们指出了导致能量和自由能计算对QM区域大小敏感的可能原因，以及潜在的影响。

更新日期：2018-02-15

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