Base pair step , conformation

As shown by Turner et fluorescence experiments using a 5 -pyrenylated oligonucleotides have aided the determination of rate constants and equilibrium constants that define (a) the initial base-pairing step in substrate binding, (b) the so-called docking step that reflects a substrate-induced conformational step, and (c) the bond cleavage step per se. The scheme shown in Fig. 3 represents a beautiful example of Koshland s induced-fit model at work in ribozyme action. 

The twists at the A5 G6 and G6 G7 and the slide at the G7 C8 base pair steps for the cisplatinated DNA-HMG complex are much closer to those of the cisplatinated adduct than the oxaliplatinated form. There is a particular biological significance for the conformational difference in the slide at the G7 C8 base pair step, as both the affinity of the HMG domain for the cisplatinated adduct and the ability of the HMG domain to discriminate between cisplatinated and oxaliplatinated DNA adducts are highly dependent on the base of the 3 side of the adduct. The conformational characteristics may facilitate the recognition of the cisplatinated from oxaliplatinated adducts by the HMG domain. 

It is now well known that certain base sequences lead to intrinsic curvature of duplex DNA. This is notably the case for tracts of four or more AT base pairs placed so that they occur in phase with the helical repeat of the duplex. This leads to the conclusion that certain base pair steps, or certain base pair tracts, should be associated with specific conformations able to deflect the axis of the double helix. An early analysis by Trifonov and Sussman showed that AA (and TT) steps had a clear tendency to be separated from one another by one helical turn within nucleosome binding sequences. Gel mobility studies, cyclization experiments and electron microscopy all subsequently confirmed that sequences containing repeated A-tracts were indeed intrinsically curved. Since this time other sequences have also been shown to produce curvature, although the effect of repeated AA steps still appears to be dominant. 

Fig.1 The six step parameters that define the conformation of a Watson-Crick base pair inDNA...

This limitation has been overcome with a special NDDO-HT parameterization for calculating hole coupling matrix elements in DNA-related systems [72]. As reference data, coupling matrix elements were calculated for a set of 130 structures of WCP dimers with different step parameters at the HF/6-31G level. As discussed below in more detail, electronic couplings between neighboring pairs are extremely sensitive to conformational fluctuations of the DNA structure. For instance, the matrix element between base pairs in... 

The electronic couplings in DNA r-stacks are very sensitive to conformational changes [31]. CT matrix elements were found to be very responsive to variations in the mutual positions of base pairs. As an example, let us compare the electronic couplings calculated for different conformations of the duplex [(GC),(GC)] (Table 4) [41]. In addition to the reference structure with a base-pair arrangement as in ideal B-DNA, we studied 12 distorted configurations each of them differed from the reference by a single step pa-... 

Tn orcTer to extend these conformational energy studies to the analysis of multi-stranded nucleic acid systems, it is necessary to devise a procedure to identify the arrangements of the polynucleotide backbone that can acconmodate double, triple, and higher order helix formation. As a first step to this end, a computational scheme is offered here to identify the double helical structures compatible with given base pairing schemes. 

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