查尔酮异构酶催化查尔酮向柚皮素的转化，作为类黄酮生物合成途径的一部分。整体反应通过底物的构象变化发生，然后进行化学反应，因此是分析当前酶催化理论的一个很好的例子。我们在这里对该酶的构象预平衡和两种不同底物的化学步骤进行了详细的理论研究。使用混合量子力学/分子力学势，根据平均力的势获得自由能分布。与水溶液中的对应物平衡和反应相比，酶的作用变得清晰。该酶不仅有利于降低相应的活化自由能的化学反应，而且还将底物的构象平衡向反应形式转移。这些结果,这可以根据在底物和环境之间的活性位点中建立的静电相互作用来合理化，同意酶催化的更一般的观点。据此,设计用于适应反应过渡态的活性位点也会对反应物状态产生影响，稳定那些在几何和/或电子上更接近过渡结构的形式。
Chalcone isomerase catalyzes the transformation of
chalcone to naringerin as a part of flavonoid biosynthetic pathways. The global reaction takes place through a conformational change of the substrate followed by chemical reaction, being thus an excellent example to analyze current theories about enzyme catalysis. We here present a detailed theoretical study of the enzymatic action on the conformational pre-equilibria and on the chemical steps for two different substrates of this enzyme. Free-energy profiles are obtained in terms of potentials of mean force using hybrid quantum mechanics/molecular mechanics potentials. The role of the enzyme becomes clear when compared to the counterpart equilibria and reactions in aqueous solution. The enzyme does not only favor the chemical reaction lowering the corresponding activation free energy but also displaces the conformational equilibria of the substrates toward the reactive form. These results, which can be rationalized in terms of the electrostatic interactions established in the active site between the substrate and the environment, agree with a more general picture of enzyme catalysis. According to this, an active site designed to accommodate the transition state of the reaction would also have consequences on the reactant state, stabilizing those forms which are geometrically and/or electronically closer to the transition structure.
