Proton chemical shift prediction of A·A mismatches in B-DNA duplexes

Abstract

A proton chemical shift prediction method has been developed for double helical DNAs containing A.A mismatches. This method makes use of the chemical shift prediction scheme for normal B-DNA duplexes developed by Altona and co-workers and a set of A.A mismatch triplet chemical shift values and corrections factors extracted from reference sequences. The triplet values are used for predicting chemical shifts of A.A mismatches whereas the normal B-DNA chemical shifts and correction factors are used for the flanking residues of A.A mismatches. Both 5'- and 3'-correction factors have been determined from the chemical shift differences upon replacing the A.A mismatch in a duplex with an A.T base pair. Based on 560 sets of predicted and experimental chemical shifts, the overall prediction accuracy for various types of protons has been determined to be 0.07 ppm with an excellent correlation coefficient of 0.9996.

NMR proton chemical shift prediction of T·T mismatches in B-DNA duplexes

“…Based on the nearest neighbor model and base pair replacement approach that were successfully established and applied in developing the chemical shift prediction method for AÁA mismatches [22], we attempted to extend our prediction scheme to develop chemical shift prediction method for TÁT mismatches. Using the base pair replacement approach [22], the predicted chemical shift of X in the XTY triplet will be equal to the chemical shift of X in the corresponding normal B-DNA with a nearest 5 0 -G and 3 0 -T (Fig.…”

“…Using the base pair replacement approach [22], the predicted chemical shift of X in the XTY triplet will be equal to the chemical shift of X in the corresponding normal B-DNA with a nearest 5 0 -G and 3 0 -T (Fig. 1c) plus a 5 0 -correction factor (5 0 -D TT/TA ), which accounts for the effect in replacing the T-A base pair with a TÁT mismatch (Fig.…”

“…Chemical shift prediction methods have been established for random coil DNA [16][17][18], double-helical B-DNA [19][20][21], B-DNA containing AÁA mismatches [22], and RNA [23]. Two major approaches have been commonly used to predict chemical shifts of nucleic acids.…”

“…The chemical shift difference obtained using this approach provides no detailed information on conformational differences but the developed method has been shown to be more precise and accurate [21]. A semi-empirical approach has also been applied to DNA and RNA [20,23] and sequence triplets have been shown to define proton chemical shifts of the middle nucleotide quite precisely [21][22][23].…”

“…Recent NMR studies have also shown the formation of TÁT mismatches in both the hairpin and dumbbell structures of tetranucleotide CCTG repeat sequences [55]. Previously, we have employed the nearest neighbor model and base pair replacement approach successfully to establish a method that allows excellent proton chemical shift prediction of AÁA mismatches in B-DNA duplexes [22]. In this study, we further investigate the general applicability of the same scheme for other types of DNA mismatches by developing a chemical shift prediction method for TÁT mismatches.…”