Elucidating the binding mechanism of Hoechst 33258 to a DNA duplex

Abstract

Small molecules binding to DNA are prevalent in biology and anticancer and antibiotic therapeutics. Although there has been success in drug development, how small molecules bind DNA remains largely unknown. Here, we employ molecular dynamics (MD) simulations with the enhanced sampling method weighted ensemble to generate fully continuous binding events of a minor groove binder Hoechst 33258 (H33258) to a DNA duplex d(CGC AAA TTT GCG)2. H33258 is a well-studied molecule known to bind to adenine and thymine-rich sequences with high affinity.