Klebe G, Böhm H J
BASF AG, Hauptlaboratorium, Ludwigshafen.
J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):459-73. doi: 10.3109/10799899709036621.
Understanding of non-covalent interactions in protein-ligand complexes is essential in modern biochemistry and should contribute toward the discovery of new drugs. The affinity of a ligand toward its receptor falls into a range of 10-80 kJ/mol. It is related to the binding constant and corresponds to a free energy. Accordingly enthalpic and entropic effects determine binding affinity. Hydrogen bonds and lipophilic contacts are the most important contributions to protein-ligand interactions. They are governed by changes in entropy and enthalpy. Solvation and desolvation effects either of the ligand and the protein binding site play a key role in the binding process. Prerequisite for a quantitative description and subsequently for a prediction of protein-ligand interactions is a partitioning in additive group contributions. In many cases, this additivity seems to be a good approximation, however, phenomena such as conformational pre-organizations give rise for a non-additive behavior. Flexibility and mobility of the bound ligand influence binding affinity. The rare experiments separating enthalpic and entropic contributions to the binding affinity sometimes reveal surprisings results, e.g. the loss of a hydrogen bond parallels with a loss in entropy.
了解蛋白质-配体复合物中的非共价相互作用在现代生物化学中至关重要，并且应该有助于新药的发现。配体对其受体的亲和力在10-80 kJ/mol范围内。它与结合常数相关，对应于自由能。因此，焓效应和熵效应决定结合亲和力。氢键和疏水相互作用是蛋白质-配体相互作用的最重要贡献。它们受熵和焓变化的支配。配体和蛋白质结合位点的溶剂化和去溶剂化效应在结合过程中起关键作用。对蛋白质-配体相互作用进行定量描述并随后进行预测的前提是将其划分为加和基团贡献。在许多情况下，这种加和性似乎是一个很好的近似值，然而，诸如构象预组织等现象会导致非加和行为。结合配体的灵活性和流动性会影响结合亲和力。将焓和熵对结合亲和力的贡献分开的罕见实验有时会揭示出令人惊讶的结果，例如氢键的丧失与熵的丧失同时发生。
