Spermine Binding to GC-Rich DNA: Experimental and Theoretical Studies

Abstract

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 deduce a mechanism for the experimentally observed cooperativity of spermine binding to poly(dGdC)2.