Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, Florida 34987, USA.
Curr Pharm Des. 2013;19(12):2138-47. doi: 10.2174/1381612811319120002.
Inhibition of DNA methyltransferases (DNMTs) is a promising approach for the therapeutic treatment of cancer and other diseases. In this work, we review the recent progress on the molecular modeling and virtual screening toward the identification of key structural features associated with the enzyme inhibitory action of active compounds and to identify DNMT inhibitors with novel molecular scaffolds. We discuss the molecular modeling with the co-factor binding site using a recent crystallographic structure of the methyltransferase domain of human DNMT1. We also review the emerging synergy of molecular modeling and chemoinformatic approaches applied to epigenetic therapies targeting DNMTs.
抑制 DNA 甲基转移酶（DNMTs）是治疗癌症和其他疾病的一种很有前途的方法。在这项工作中，我们回顾了近年来在分子建模和虚拟筛选方面的最新进展，以确定与活性化合物酶抑制作用相关的关键结构特征，并鉴定具有新型分子骨架的 DNMT 抑制剂。我们使用最近获得的人 DNMT1 甲基转移酶结构域的晶体结构讨论了共因子结合位点的分子建模。我们还回顾了分子建模与化学生信学方法在针对 DNMT 的表观遗传学治疗中的协同作用。
