Spermine binding to GC-rich DNA: experimental and theoretical studies.

The DNA binding of spermine has been studied using experimental and computational approaches. Spermine blocks 5'-GC interstrand crosslinking by 2,5-diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTCCAAGATGCATCAGATG 5'-CATCTGATGCATCTTGGAAG (where the underlined nucleotide bases represent the crosslinking site). Molecular dynamics simulations suggest that this is a result of preferential spermine binding at the 5'-GC major groove site of the oligonucleotide. A further simulation with a GC-alternating sequence shows a similar preference for the 5'-GC step. In a simulation including multiple spermine molecules, occupation of alternate 5'-GC steps occurred. From this, we deduced a mechanism for the experimentally observed cooperativity of spermine binding to poly(dGdC)2.