School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, P. R. China.
State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, P. R. China.
J Chem Inf Model. 2017 Jul 24;57(7):1535-1547. doi: 10.1021/acs.jcim.7b00022. Epub 2017 Jun 16.
In this work, we tentatively propose that the hydrogen-bonding strength E (referring to the minimal hydrogen-bonding energy) and its corresponding hydrogen-bond (HB) distance (referring to the optimal HB distance d) for simple mono-HB systems have an exponential relationship on the basis of MP2 and DFT computational results. We take a step further and propose that the hydrogen-bonding indices of the donor (I) and acceptor (I), reflecting their intrinsic contributions to hydrogen-bonding strength, also have an exponential relation with the hypothetical effective hydrogen-bond radii of the donor (r) and acceptor (r), respectively. On the basis of extensive quantum-mechanical calculations, relevant assumptions about the hydrogen-bonding index are rationalized. Moreover, the hydrogen-bonding index is also suggested as an additional prefiltering criterion for virtual screening besides the widely accepted Lipinski's rule of five. Finally, a "Hydrogen-Bond Index Estimator (HBIE)" module has been implemented in our Visual Force Field Derivation Toolkit (VFFDT) program to approximately and rapidly estimate the hydrogen-bonding indices of any small molecules in batch and screen possible stronger donors or acceptors from the small-molecule database. To the best of our knowledge, the concept of the hydrogen-bonding index and its potential application are proposed here for the first time.
在这项工作中，我们基于 MP2 和 DFT 计算结果，初步提出氢键的键能 E（指最小氢键能）及其对应的氢键距离（指最优氢键距离 d）与简单单氢键体系之间存在指数关系。在此基础上，我们进一步提出供体（I）和受体（I）的氢键指数，分别反映了它们对氢键强度的内在贡献，也与假设的供体（r）和受体（r）的有效氢键半径呈指数关系。基于广泛的量子力学计算，对氢键指数的相关假设进行了合理化。此外，氢键指数也被建议作为除了广泛接受的 Lipinski 五规则之外的虚拟筛选的附加预筛选标准。最后，在我们的可视化力场推导工具包（VFFDT）程序中实现了一个“氢键指数估算器（HBIE）”模块，以便批量估算任何小分子的氢键指数，并从小分子数据库中筛选出可能更强的供体或受体。据我们所知，这里首次提出了氢键指数的概念及其潜在应用。
