Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul;41(Web Server issue):W56-62.
doi: 10.1093/nar/gkt437. Epub 2013 May 22.

DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale

Tianyin Zhou  1 , Lin Yang, Yan Lu, Iris Dror, Ana Carolina Dantas Machado, Tahereh Ghane, Rosa Di Felice, Remo Rohs
Affiliations

DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale

Tianyin Zhou et al. Nucleic Acids Res. 2013 Jul.

Abstract

We present a method and web server for predicting DNA structural features in a high-throughput (HT) manner for massive sequence data. This approach provides the framework for the integration of DNA sequence and shape analyses in genome-wide studies. The HT methodology uses a sliding-window approach to mine DNA structural information obtained from Monte Carlo simulations. It requires only nucleotide sequence as input and instantly predicts multiple structural features of DNA (minor groove width, roll, propeller twist and helix twist). The results of rigorous validations of the HT predictions based on DNA structures solved by X-ray crystallography and NMR spectroscopy, hydroxyl radical cleavage data, statistical analysis and cross-validation, and molecular dynamics simulations provide strong confidence in this approach. The DNAshape web server is freely available at http://rohslab.cmb.usc.edu/DNAshape/.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Pentamer model for HT prediction and validation of the HT approach using Fis-binding sites. (A) MC predictions were mined with a sliding-pentamer window, and a query table of average structural features characterizing either the central bp (e.g., MGW) or the two central bp steps (e.g., Roll) of a pentamer was assembled to predict the structural features of any length of DNA. (B) HT predictions of the average MGW over the five central bp of seven Fis-binding sites (6) correlate with the logarithm of binding affinity (red). The predictive power further increases for six sequences (blue) after one sequence with a TpA step is removed (F25; Supplementary Table S2). The MGW as a function of sequence is predicted for (C) high-affinity (Kd = 0.2 nM) and (D) low-affinity (Kd = 140 nM) binding sites using the HT (blue) and MC (red) approaches and compared with X-ray data (green) of protein–DNA complexes (PDB IDs in Supplementary Materials and Methods). The large positive MGW values observed in X-ray data are usually due to crystal packing and are not observed in solution. Spearman’s rank correlation coefficients (ρ) demonstrate the statistical similarity between the predicted and experimental MGW profiles.
Figure 2.
Figure 2.
Validation of HT predictions using the Dickerson dodecamer. Structural features (A) MGW, (B) Roll, (C) ProT and (D) HelT of the palindromic Dickerson dodecamer are predicted with the HT (blue) and MC (red) approaches. These features are compared with the symmetrized average profiles derived from eight crystal structures (green) without chemical modifications and the average profiles derived from 10 NMR structures (purple) using RDC (PDB IDs in Supplementary Table S3). The more extreme HelT values observed in X-ray data are usually due to crystal packing and are not observed in solution. Spearman’s rank correlation coefficients (ρ) demonstrate the statistical similarity between the predicted and experimental structural feature profiles, which we symmetrized according to the palindromic sequence.
Figure 3.
Figure 3.
Validation of HT predictions using protein–DNA binding sites. (A–F) MGW for the DNA binding sites of six proteins, for which DNA shape readout was previously observed (1), are predicted using the HT (blue) and MC (red) approaches and compared with X-ray data (green) of protein–DNA complexes (PDB IDs in Supplementary Materials and Methods). The large positive MGW values observed in X-ray data are usually due to crystal packing and are not observed in solution. Therefore, qualitative MGW patterns (minima versus maxima) are the more essential characteristics compared to actual values. The MGW minima correlate with regions of enhanced negative electrostatic potential, thus providing binding sites for basic arginine side chains (1). Spearman’s rank correlation coefficients (ρ) demonstrate the statistical similarity between the predicted and experimental MGW profiles.
Figure 4.
Figure 4.
Validation of HT predictions using nucleosome binding sites. The MGW is predicted for (A) 23 076 yeast and (B) 25 654 fly in vivo nucleosome binding sites (22,23), and its average is compared with previously published OH-cleavage data derived from ORChID2 (19). HT predictions of MGW (blue) and OH-cleavage intensity (orange) are highly correlated, both revealing the 10-bp periodicity observed in dinucleotide propensity (1). Spearman’s rank correlation coefficients (ρ) demonstrate the statistical similarity between the predicted MGW and OH-cleavage intensity profiles.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. The role of DNA shape in protein-DNA recognition. Nature. 2009;461:1248–1253. - PMC - PubMed
    1. Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu. Rev. Biochem. 2010;79:233–269. - PMC - PubMed
    1. Joshi R, Passner JM, Rohs R, Jain R, Sosinsky A, Crickmore MA, Jacob V, Aggarwal AK, Honig B, Mann RS. Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell. 2007;131:530–543. - PMC - PubMed
    1. Gordan R, Shen N, Dror I, Zhou T, Horton J, Rohs R, Bulyk ML. Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape. Cell Rep. 2013;3:1093–1104. - PMC - PubMed
    1. West SM, Rohs R, Mann RS, Honig B. Electrostatic interactions between arginines and the minor groove in the nucleosome. J. Biomol. Struct. Dyn. 2010;27:861–866. - PMC - PubMed

Publication types