Overstretching of a 30 bp DNA duplex studied with steered molecular dynamics simulation: effects of structural defects on structure and force-extension relation.
Single-molecule experiments on polymeric DNA show that the molecule can be overstretched at nearly constant force by about 70% beyond its relaxed contour length. In this publication we use steered molecular dynamics (MD) simulation to study the effect of structural defects on force-extension curves and structures at high elongation in a 30 base pair duplex pulled by its torsionally unconstrained 5' -5' ends. The defect-free duplex shows a plateau in the force-extension curve at 120 pN in which large segments with inclined and paired bases ("S-DNA") near both ends of the duplex coexist with a central B-type segment separated from the former by small denaturation bubbles. In the presence of a base mismatch or a nick, force-extension curves are very similar to the ones of the defect-free duplex. For the duplex with a base mismatch, S-type segments with highly inclined base pairs are not observed; rather, the overstretched duplex consists of B-type segments separated by denaturation bubbles. The nicked duplex evolves, via a two-step transition, into a two-domain structure characterized by a large S-type segment coexisting with several short S-type segments which are separated by short denaturation bubbles. Our results suggest that in the presence of nicks the force-extension curve of highly elongated duplex DNA might reflect locally highly inhomogeneous stretching.
Universität Konstanz, Fachbereich Physik, 78457 Konstanz, Germany.
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D020137:Base Pair Mismatch; D001483:Base Sequence; D001696:Biomechanical Phenomena; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation
D004247:DNA