The predominant binding mode of Palmatine to DNA

Palmatine is a protoberberine alkaloid, which may produce singlet oxygen under visible light irradiation and binds to DNA. The fact that singlet oxygen activation in palmatine may be triggered by environmental conditions, and in particular its interaction with nucleic acids, makes it a most suitable candidate for photodynamic therapy and DNA-targeted non-invasive anticancer strategies. Despite these remarkable properties the actual binding mode between palmatine and DNA has not been resolved, yet. Its elucidation has, indeed, led to contrasting hypothesis. In this contribution by using long-range molecular dynamic simulations and enhanced sampling approaches, we unequivocally identify that intercalation is the dominant binding mode of palmatine with DNA, from either a thermodynamic and kinetic point of view. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/613446v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1f30e43org.highwire.dtl.DTLVardef@2d5e04org.highwire.dtl.DTLVardef@776b2aorg.highwire.dtl.DTLVardef@1ca206_HPS_FORMAT_FIGEXP M_FIG C_FIG