Seite - 7 - in Charge Transport in DNA - Insights from Simulations

ThestateofknowledgeofDNAstretching in2000wassummarizedintworeviews. [24, 25]At that time, a dispute on the nature of the overstretched state of dsDNA started, and it is in fact still going on. In contrast to the proposal of S-DNA, theoverstretchingprofileofDNAwasattributed to force-induceddehybridization basedonthermodynamicobservations.[26]Sincethen,reportshavebeenconstantly appearing against,[27] as well as in favor of the thermally induced melting.[28] Importantly, the nature of the overstretched state of DNA probably depends on the rate of stretching. A dsDNA oligomer was reported to dehybridize under a certain critical stretching rate,whereas a transition to S-DNAwasobserved above this threshold.[29] Further, DNA is observedmore stablewith 3’–3’ pulling than with5’–5’, and itwaspointedout that the relevant structuresaredifferent.[30]Two distinctoverstretchedDNAstateswereshownyetagain tooccur,[31]dependingon conditions likeDNA sequence, salt concentration and temperature. An excellent discussion of the state of the art on the DNA overstretching and of the current knowledge is given inRef. [32]. As for themolecularmodeling,quitea fewstudieson theoverstretching transition ofdsDNAappeared.[33–37] Theyall dealwithdsDNAoligomers ofup to 30base pairs being stretched in different ways, pulling either the 5’ ends, the 3’ ends or eventually all ends of the double strand. Inevitably, the still substantial computa- tional costofatomisticmoleculardynamics (MD)simulationmakes the timescales probedintheexperiments inaccessible. Thepreviouslyreporteddependenceof the conformationofoverstretchedDNAonthe loadingrate is thusan issue thathas to be taken intoaccountwhen interpreting theoutcomeofMDsimulations. At this point, thedependence ofCT inDNAon the conformationof themolecule canbe investigatedwithcomputationalmethodsconveniently. Electronic structure of overstretched DNA’ was the topic of an early study[38] dealing with a single sequence and static structures. Surprising response of CT efficiency on theDNA conformationwas found,[39] however,with a simplified stretching/twisting reac- tion coordinate. Indeed, it has long been known that the dynamic character of molecular structure has to be taken into account instead of static structures.[40] Especially formore complexmolecules likeDNA, the structuraldynamics and the molecular environmentplaydecisive roles,[41] bringing theseeffects into the focus of thoroughtheoretical investigation.[42–46]Thus, thecomputationalapproachhas to involve a plausible description ofDNAconformation and its fluctuationunder 7 Introduction