DNA methylations are carried out by DNA methyltransferases (DNMTs) that are key enzymes during gene expression. Many chemicals, including pesticides, have shown modulation of epigenetic functions by inhibiting DNMTs. In this work, human DNMTs were evaluated as a potential target for pesticides through virtual screening of 1038 pesticides on DNMT1 (3SWR) and DNMT3A (2QRV). Molecular docking calculations for DNMTs-pesticide complexes were performed using AutoDock Vina. Binding-affinity values and contact patterns were employed as selection criteria of pesticides as virtual hits for DNMTs. The best three DNMT-pesticides complexes selected according to their high absolute affinity values (kcal/mol), for both DNMT1 and DNMT3A, were flocoumafen (−12.5; −9.9), brodifacoum (−12.4; −8.4) and difenacoum (−12.1; −8.7). These chemicals belong to second-generation rodenticides. The most frequent predicted interacting residues for DNMT1-pesticide complexes were Trp1170A, Phe1145A, Asn1578A, Arg1574A and Pro1225A; whereas for DNMT3A those were Arg271B, Lys740A, and Glu303B. These results suggest that rodenticides used for pest control are potential DNMT ligands and therefore, may modulate DNA methylations. This finding has important environmental and clinical implications, as epigenetic pathways are critical in many biochemical processes leading to diseases.

DNA甲基化由DNA甲基转移酶（DNMT）进行，DNMT是基因表达过程中的关键酶。许多化学物质（包括农药）通过抑制DNMT表现出表观遗传功能的调节作用。在这项工作中，通过在DNMT1（3SWR）和DNMT3A（2QRV）上对1038种农药进行虚拟筛选，评估了人类DNMT作为农药的潜在目标。使用AutoDock Vina对DNMT-农药复合物进行分子对接计算。结合亲和力值和接触模式被用作农药选择标准，成为DNMT的虚拟命中。根据DNMT1和DNMT3A的高绝对亲和力值（kcal / mol）选择的最好的三种DNMT农药复合物是flocoumafen（-12.5; -9.9），brodifacoum（-12.4; -8.4）和difenacoum（-12.1） ; −8.7）。这些化学物质属于第二代灭鼠剂。DNMT1农药复合物最常见的预测相互作用残基为Trp1170A，Phe1145A，Asn1578A，Arg1574A和Pro1225A。DNMT3A是Arg271B，Lys740A和Glu303B。这些结果表明，用于害虫防治的灭鼠剂是潜在的DNMT配体，因此可能调节DNA甲基化。这一发现具有重要的环境和临床意义，因为表观遗传途径在导致疾病的许多生化过程中至关重要。这些结果表明，用于害虫防治的灭鼠剂是潜在的DNMT配体，因此可能调节DNA甲基化。这一发现具有重要的环境和临床意义，因为表观遗传途径在导致疾病的许多生化过程中至关重要。这些结果表明，用于害虫防治的灭鼠剂是潜在的DNMT配体，因此可能调节DNA甲基化。这一发现具有重要的环境和临床意义，因为表观遗传途径在导致疾病的许多生化过程中至关重要。