Structure-based virtual screening and molecular dynamics simulations of FDA-approved drugs targeting MALAT1

In recent decades, RNA has emerged as an attractive target for the discovery of new small molecules with a wide range of pharmacological activities. Notably, long noncoding RNAs (lncRNAs) have been widely implicated in cancer development. Among these, the overexpression of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been linked to various types of cancer. In light of this, we carried out a structure-based virtual screening (SBVS) of the FDA-approved drug database towards the crystallographic structure of the triple-helical stability element at the 3’-end of MALAT1. Hence, the thermodynamic analysis led to the selection of five drugs for their evaluation through Molecular Dynamics simulations (MDs). Chlorhexidine and kanamycin emerged as the most promising molecules due to their optimal free energy of binding. In particular, during the MDs, chlorhexidine exhibited the most unstable behavior, demonstrating the ability to explore a wide range of conformations. (Figure presented.)