While the induced-fit of a ligand towards an enzyme is pivotally dictated by intermolecular hydrogen bonds between the small molecule and amino acid residues in the binding site, the role of intramolecular hydrogen bond as contributing interaction for a bioactive conformation is not well understood. This work reports a theoretical conformational analysis of a thymidine kinase enzyme ligand (NMF) that is prone to experience an F⋯HO intramolecular hydrogen bond, inside and outside the biological binding site. This interaction stabilizes the most favorable conformations of NMF in the gas phase and, although it can be disrupted in a biological environment due to intermolecular hydrogen bonds in some cases, these interactions are competitive in other systems. Therefore, an intramolecular hydrogen bond can affect the conformational likeliness most related to the bioactivity. Moreover, isolated conformations governed by this interaction cannot be unequivocally used to generate molecular descriptors in 3D-QSAR (Quantitative Structure-Activity Relationships), since the bioactive conformation may not be determined only by intramolecular interactions.

虽然配体对酶的诱导适应性是由小分子与结合位点中的氨基酸残基之间的分子间氢键决定的，但人们对分子内氢键作为生物活性构象的相互作用的作用还不甚了解。这项工作报告了对胸苷激酶酶配体（NMF）的理论构象分析，该结构易于在生物结合位点的内部和外部经历F⋯HO分子内氢键。这种相互作用稳定了气相中最有利的NMF构象，尽管在某些情况下由于分子间氢键在生物环境中可能会破坏NMF，但这些相互作用在其他系统中具有竞争性。因此，分子内氢键可影响与生物活性最相关的构象似然性。而且，受此相互作用支配的分离的构象不能明确地用于在3D-QSAR（定量结构-活性关系）中生成分子描述符，因为生物活性构象可能不仅由分子内相互作用决定。