Theoretical calculation of hydrogen-bonding strength for drug molecules
Theoretical calculation of hydrogen-bonding strength for drug molecules
复制标题
DOI：
10.1021/ct0600262
复制
发表时间：
2006-05-01
影响因子：
5.5
通讯作者：
Hao, MH
中科院分区：
文献类型：
--
作者：
Hao, MH
氢键是药物分子与受体之间相互作用的重要形式。我们在这里提出了一种计算方法，用于准确地预测不同受体相对于给定的供体或反之亦然的氢键强度。该方法基于氢键给体和受体之间相互作用能的量子化学DFT计算。一个很好的线性相关性之间观察到的计算的氢键能和实验测得的氢键常数log K，在各种已知的氢键受体和供体。这些结果不仅表明了这种方法的预测能力，但也揭示了确定不同受体相对于给定供体的实验测得的氢键常数的大小的因素，这表明主要是氢键能的贡献。该方法可用于评价药物设计中空间干扰和抑制剂结合几何构型对氢键强度的影响。
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 K, 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.