Solution structure of the dodecamer d-(CATGGGCC-CATG)(2) is B-DNA. Experimental and molecular dynamics study

The DNA duplex d-(CATGGGCCCATG)(2) has been studied in solution by FTIR. NM R and CD. The experimental approaches have been complemented by series of l arge-scale unrestrained molecular dynamics simulation with explicit inclusi on of solvent and counterions . Typical proton-proton distances extracted f rom the NMR spectra and the CD spectra are completely in agreement with sli ghtly modified B-DNA. By molecular dynamics simulation, starting from A-typ e sugar pucker, a spontaneous repuckering to B-type sugar pucker was observ ed. Both experimental and theoretical approaches suggest for the dodecamer d-(CATGGGCCCATG)(2) under solution conditions puckering of all 2'-deoxyribo se residues in the south conformation (mostly C2'-endo) and can exclude sig nificant population of sugars in the north conformation (C3'-endo). NMR. FT IR and CD data are in agreement with a B-form of the dodecamer in solution. Furthermore, the duplex shows a cooperative B-A transition in solution ind uced by addition of trifluorethanol. This contrasts a recently published cr ystal structure of the same oligonucleotide found as an intermediate betwee n B- and A-DNA where 23 out of 24 sugar residues were reported to adopt the north (N-type) conformation (CY-endo) like in A-DNA (Ng, H. L., Kopka, M. L. and Dickerson, R. E., Proc. Natl. Acad. Sci. U S A 97, 2035-2039 (2000)) . The simulated structures resemble standard B-DNA. They nevertheless show a moderate shift towards A-type stacking similar to that seen in the crysta l, despite the striking difference in sugar puckers between the MD and X-ra y structures. This is in agreement with preceding MD reports noticing speci al stacking features of G-tracts exhibiting a tendency towards the A-type s tacking supported by the CD spectra also reflecting the G-tract stacking. M D simulations reveal several noticeable local conformational variations, su ch as redistribution of helical twist and base pair roll between the centra l GpC steps and the adjacent G-tract segments, as well as a substantial hel ical twist variability in the CpA(TpG) steps combined with a large positive base pair roll. These local variations are rather different from those see n in the crystal. The results are discussed in terms of recent findings of DNA structures wit h mixed features of A-DNA and B-DNA.