DNA stretching and compression: large-scale simulations of double helical structures.

Computer-simulated elongation and compression of A - and B -DNA structures beyond the range of thermal fluctuations provide new insights into high energy "activated" forms of DNA implicated in biochemical processes, such as recombination and transcription. All-atom potential energy studies of regular poly(dG).poly(dC) and poly(dA).poly(dT) double helices, stretched from compressed states of 2.0 A per base-pair step to highly extended forms of 7.0 A per residue, uncover four different hyperfamilies of right-handed structures that differ in mutual base-pair orientation and sugar-phosphate backbone conformation. The optimized structures embrace all currently known right-handed forms of double-helical DNA identified in single crystals as well as non-canonical forms, such as the original "Watson-Crick" duplex with trans conformations about the P-O5' and C5'-C4' backbone bonds. The lowest energy minima correspond to canonical A and B -form duplexes. The calculations further reveal a number of unusual helical conformations that are energetically disfavored under equilibrium conditions but become favored when DNA is highly stretched or compressed. The variation of potential energy versus stretching provides a detailed picture of dramatic conformational changes that accompany the transitions between various families of double-helical forms. In particular, the interchanges between extended canonical and non-canonical states are reminiscent of the cooperative transitions identified by direct stretching experiments. The large-scale, concerted changes in base-pair inclination, brought about by changes in backbone and glycosyl torsion angles, could easily give rise to the observed sharp increase in force required to stretch single DNA molecules more than 1.6-1.65 times their canonical extension. Our extended duplexes also help to tie together a number of previously known structural features of the RecA-DNA complex and offer a self-consistent stereochemical model for the single-stranded/duplex DNA recognition brought in register by recombination proteins. The compression of model duplexes, by contrast, yields non-canonical structures resembling the deformed steps in crystal complexes of DNA with the TATA-box binding protein (TBP). The crystalline TBP-bound DNA steps follow the calculated compression-elongation pattern of an unusual "vertical" duplex with base planes highly inclined with respect to the helical axis, exposed into the minor groove, and accordingly accessible for recognition.Significantly, the double helix can be stretched by a factor of two and compressed roughly in half before its computed internal energy rises sharply. The energy profiles show that DNA extension-compression is related not only to the variation of base-pair Rise but also to concerted changes of Twist, Roll, and Slide. We suggest that the high energy "activated" forms calculated here are critical for DNA processing, e.g. nucleo-protein recognition, DNA/RNA synthesis, and strand exchange.