To accurately simulate the inner workings of an enzyme active site with quantum mechanics (QM), not only must the reactive species be included in the model but also important surrounding residues, solvent, or coenzymes involved in crafting the microenvironment. Our lab has been developing the Residue Interaction Network Residue Selector (RINRUS) toolkit to utilize interatomic contact network information for automated, rational residue selection and QM-cluster model generation. Starting from an x-ray crystal structure of catechol-O-methyltransferase, RINRUS was used to construct a series of QM-cluster models. The reactant, product, and transition state of the methyl transfer reaction were computed for a total of 550 models, and the resulting free energies of activation and reaction were used to evaluate model convergence. RINRUS-designed models with only 200–300 atoms are shown to converge. RINRUS will serve as a cornerstone for improved and automated cheminformatics-based enzyme model design.

为了使用量子力学 (QM) 准确模拟酶活性位点的内部运作，模型中不仅必须包含反应性物质，还必须包含重要的周围残基、溶剂或辅酶参与构建微环境。我们的实验室一直在开发 Residue Interaction Network Residue Selector ( RINRUS ) 工具包，以利用原子间接触网络信息进行自动化、合理的残基选择和 QM-cluster 模型生成。从儿茶酚-O-甲基转移酶的 X 射线晶体结构开始，RINRUS用于构建一系列 QM-cluster 模型。计算了总共 550 个模型的甲基转移反应的反应物、产物和过渡态，并使用所得的活化和反应自由能来评估模型的收敛性。RINRUS设计的只有 200-300 个原子的模型显示收敛。RINRUS将作为改进和自动化的基于化学信息学的酶模型设计的基石。