Quantification of Solvent Contribution to the Stability of Noncovalent Complexes.
Quantification of Solvent Contribution to the Stability of Noncovalent Complexes.
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DOI：
10.1021/ct400404q
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发表时间：
2013-09
影响因子：
5.5
通讯作者：
H. Zhang;T. Tan;C. Hetényi;D. van der Spoel
中科院分区：
文献类型：
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作者：
H. Zhang;T. Tan;C. Hetényi;D. van der Spoel
我们介绍了一种间接的方法来估计溶剂化的非共价复合物形成的热力学通过分子动力学模拟的贡献。通过对β-环糊精（主体）与葛根素、大豆苷、大豆苷元和萘丁美酮（客体）在显式水中结合过程的平均力势和熵计算，以及从总自由能中逐步提取焓（ΔH）和熵（ΔS）项，证明了这一估计。对主客体络合热力学的详细分析表明，为了准确估计结合热力学，需要明确地考虑结合配偶体的柔性和溶剂化相关的ΔH和ΔS。从这一点以及我们先前关于结合能的溶剂依赖性的工作（Zhang et al. J. Phys. Chem. B 2012，116，12684-12693），可以得出，忽略主体或客体柔性的计算或采用隐式溶剂的计算将不能系统地预测结合自由能。这里提出的方法可以很容易地通过获得更深入的了解的机制，在解决方案中的非共价缔合。
We introduce an indirect approach to estimate the solvation contributions to the thermodynamics of noncovalent complex formation through molecular dynamics simulation. This estimation is demonstrated by potential of mean force and entropy calculations on the binding process between β-cyclodextrin (host) and four drug molecules puerarin, daidzin, daidzein, and nabumetone (guest) in explicit water, followed by a stepwise extraction of individual enthalpy (ΔH) and entropy (ΔS) terms from the total free energy. Detailed analysis on the energetics of the host-guest complexation demonstrates that flexibility of the binding partners and solvation-related ΔH and ΔS need to be included explicitly for accurate estimation of the binding thermodynamics. From this, and our previous work on the solvent dependency of binding energies (Zhang et al. J. Phys. Chem. B 2012, 116, 12684-12693), it follows that calculations neglecting host or guest flexibility, or those employing implicit solvent, will not be able to systematically predict binding free energies. The approach presented here can be readily adopted for obtaining a deeper understanding of the mechanisms governing noncovalent associations in solution.