Double‐helical DNA 1H chemical shifts: an accurate and balanced predictive empirical scheme

Abstract

Chemical shifts of exchangeable and non-exchangeable protons in double-helical B DNA fragments were collected from the literature , subjected to statistical analysis and tabulated. The tables are arranged according to the central residue involved (A, G, C and T) and to the 5 0 -and 3 0 -flanking residues (triplet model). The standard deviations in the mean (90% confidence limits) are of the order of 0.02-0.04 ppm for most protons. In addition, data on terminal residues were collected (terminal doublets) and it is shown that these shifts play a key role in the empirical determination of physically meaningful shielding/deshielding increments induced by the 5 0 -and 3 0 -flanking bases in triplets. The r.m.s. error of the shifts predicted with the aid of our new incremental scheme is 0.01-0.03 ppm. The analysis throws new light on the mechanism involved in the fraying process.

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

“…In addition, the prediction results can provide useful information for studying structure-chemical shift relationship, identifying unstructured or right-handed double helical regions, monitoring DNA-drug or DNA-protein binding, and investigating conformational details of special features in DNA structures. At present, several methods have been established to predict chemical shifts of random coil DNAs [5][6][7], double helical B-DNAs [8][9][10] and RNAs [11]. Briefly, chemical shifts can be predicted from structures using the same types of electrostatic and ring-current models that have been applied to proteins [8,9,11] or from measured chemical shifts within a set of given sequences that adopt stable and well-defined conformations [10].…”

“…At present, several methods have been established to predict chemical shifts of random coil DNAs [5][6][7], double helical B-DNAs [8][9][10] and RNAs [11]. Briefly, chemical shifts can be predicted from structures using the same types of electrostatic and ring-current models that have been applied to proteins [8,9,11] or from measured chemical shifts within a set of given sequences that adopt stable and well-defined conformations [10]. The former approach is usually preferred because it relates chemical shifts directly to conformation.…”

“…For the latter approach, no detailed information on conformational differences can be obtained once chemical shift difference is identified between predicted and experimental values. However, this approach has been shown to be more precise and accurate for predicting DNA chemical shifts [10]. A hybrid approach of the above prediction methods have also been applied to DNAs [9] and RNAs [11] and it has been found that sequence triplets define proton chemical shifts of the middle residue quite precisely [10,11].…”

“…However, this approach has been shown to be more precise and accurate for predicting DNA chemical shifts [10]. A hybrid approach of the above prediction methods have also been applied to DNAs [9] and RNAs [11] and it has been found that sequence triplets define proton chemical shifts of the middle residue quite precisely [10,11]. In order to widen the applications of DNA chemical shifts, this work aims to develop chemical shift prediction methods for DNA duplexes containing mismatches.…”

“…1b, namely duplexAAET (XAY) and duplexTAEA(XAY), which contain an AAET and TAEA base pair instead of the AAEA mismatch, respectively. Since only the nearest neighbor effect has been considered to be important in predicting proton chemical shift in B-DNA duplexes [9,10], it is expected that the effect of replacing AAET or TAEA with AAEA on the next nearest neighbor chemical shifts will be negligibly small. Therefore, the present work will focus on predicting the chemical shifts of AAEA mismatch and its flanking residues in B-DNA duplexes.…”