Hao Ming-Hong
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
J Chem Theory Comput. 2006 May;2(3):863-72. doi: 10.1021/ct0600262.
Hydrogen bond is an important type of interaction between drug molecules and their receptors. We present here a computational method for accurately predicting the hydrogen-bonding strength for different acceptors with respect to a given donor or vice versa. The method is based on quantum chemistry DFT calculation of the interaction energy between hydrogen bond donors and acceptors. An excellent linear correlation is observed between the calculated hydrogen-bonding energies and the experimentally measured hydrogen-bonding constants log Kβ on a variety of known hydrogen bond acceptors and donors. These results not only indicate the predictive power of this method but also shed light on factors that determine the magnitude of experimentally measured hydrogen-bonding constants for different acceptors with respect to a given donor, suggesting a primarily enthalpic contribution from hydrogen-bonding energy. The method can be used for evaluating the effects of steric interference and inhibitor binding geometry on hydrogen-bonding strength in drug design.
氢键是药物分子与其受体之间一种重要的相互作用类型。我们在此提出一种计算方法，用于准确预测相对于给定供体的不同受体的氢键强度，反之亦然。该方法基于对氢键供体和受体之间相互作用能的量子化学密度泛函理论（DFT）计算。在各种已知的氢键受体和供体上，计算得到的氢键能量与实验测量的氢键常数log Kβ之间观察到了极好的线性相关性。这些结果不仅表明了该方法的预测能力，还揭示了决定相对于给定供体的不同受体的实验测量氢键常数大小的因素，表明氢键能量主要有焓的贡献。该方法可用于评估空间位阻干扰和抑制剂结合几何结构对药物设计中氢键强度的影响。
