Dynamics of B-DNA on the microsecond time scale

Abstract

We present the first microsecond MD simulation of B-DNA. Trajectory shows good agreement with available data and clarifies the μs dynamics of DNA. The duplex is sampling the B-conformation, but many relevant local transitions are found, including S → N repuckers (up to 7 N-sugars are found simultaneously), local BII transitions (15% of the dinucleotides are in BII-form; some of these forms are stable for up to 7 ns), and sequence-dependent α/γ transitions (happening in the 7-50 ns time scale, and being stable for up to 80 ns). Partial and total openings are often detected, but no base flipping is found. A·T openings happen after amplification of propeller twist movements, while G·C pairs (which can be opened for up to 1 ns) are opened by a complex mechanism which is often catalyzed by cations. A high affinity Na+ binding site is found in the center of the minor groove. Access to this site by cations is difficult (average entry time 400 ns), but once inside, the ion remains for long periods of time (10-15 ns), producing a sizable narrowing of the minor groove. The essential dynamics of DNA fits well with the pattern of deformation needed to (i) sample uncommon right-handed forms and (ii) sample conformations adopted by DNA when bound to proteins. Clearly, DNA has evolved to be not only a stable structure able to maintain and transmit the genetic information but also a flexible entity whose intrinsic pattern of deformability matches its functional needs. © 2007 American Chemical Society.