Automatic Workflow for the Classification of Local DNA Conformations

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2013 Jun 27

PMID 23800225

Citations 11

Authors

Petr cech

Jaromir Kukal

Jiri cerny

Bohdan Schneider

Daniel Svozil

Affiliations

Soon will be listed here.

Abstract

Background: A growing number of crystal and NMR structures reveals a considerable structural polymorphism of DNA architecture going well beyond the usual image of a double helical molecule. DNA is highly variable with dinucleotide steps exhibiting a substantial flexibility in a sequence-dependent manner. An analysis of the conformational space of the DNA backbone and the enhancement of our understanding of the conformational dependencies in DNA are therefore important for full comprehension of DNA structural polymorphism.

Results: A detailed classification of local DNA conformations based on the technique of Fourier averaging was published in our previous work. However, this procedure requires a considerable amount of manual work. To overcome this limitation we developed an automatic classification method consisting of the combination of supervised and unsupervised approaches. A proposed workflow is composed of k-NN method followed by a non-hierarchical single-pass clustering algorithm. We applied this workflow to analyze 816 X-ray and 664 NMR DNA structures released till February 2013. We identified and annotated six new conformers, and we assigned four of these conformers to two structurally important DNA families: guanine quadruplexes and Holliday (four-way) junctions. We also compared populations of the assigned conformers in the dataset of X-ray and NMR structures.

Conclusions: In the present work we developed a machine learning workflow for the automatic classification of dinucleotide conformations. Dinucleotides with unassigned conformations can be either classified into one of already known 24 classes or they can be flagged as unclassifiable. The proposed machine learning workflow permits identification of new classes among so far unclassifiable data, and we identified and annotated six new conformations in the X-ray structures released since our previous analysis. The results illustrate the utility of machine learning approaches in the classification of local DNA conformations.

Citing Articles

3dDNAscoreA: A scoring function for evaluation of DNA 3D structures.

Zhang Y, Yang C, Xiong Y, Xiao Y Biophys J. 2024; 123(17):2696-2704.

PMID: 38409781 PMC: 11393702. DOI: 10.1016/j.bpj.2024.02.018.

Accurate prediction of B-form/A-form DNA conformation propensity from primary sequence: A machine learning and free energy handshake.

Gupta A, Kulkarni M, Mukherjee A Patterns (N Y). 2021; 2(9):100329.

PMID: 34553171 PMC: 8441556. DOI: 10.1016/j.patter.2021.100329.

Ion Binding Properties and Dynamics of the 2 G-Quadruplex Using a Polarizable Force Field.

Ratnasinghe B, Salsbury A, Lemkul J J Chem Inf Model. 2020; 60(12):6476-6488.

PMID: 33264004 PMC: 7775346. DOI: 10.1021/acs.jcim.0c01064.

Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments.

Poltev V, Anisimov V, Dominguez V, Gonzalez E, Deriabina A, Garcia D J Mol Model. 2018; 24(2):46.

PMID: 29392428 DOI: 10.1007/s00894-018-3589-8.

A DNA structural alphabet provides new insight into DNA flexibility.

Schneider B, Boaeikova P, Necasova I, cech P, Svozil D, cerny J Acta Crystallogr D Struct Biol. 2018; 74(Pt 1):52-64.

PMID: 29372899 PMC: 5786007. DOI: 10.1107/S2059798318000050.

References

Nikolova E, Bascom G, Andricioaei I, Al-Hashimi H . Probing sequence-specific DNA flexibility in a-tracts and pyrimidine-purine steps by nuclear magnetic resonance (13)C relaxation and molecular dynamics simulations. Biochemistry. 2012; 51(43):8654-64. PMC: 3676944. DOI: 10.1021/bi3009517. View

Jain A, Wang G, Vasquez K . DNA triple helices: biological consequences and therapeutic potential. Biochimie. 2008; 90(8):1117-30. PMC: 2586808. DOI: 10.1016/j.biochi.2008.02.011. View

Tisne C, Hantz E, Hartmann B, Delepierre M . Solution structure of a non-palindromic 16 base-pair DNA related to the HIV-1 kappa B site: evidence for BI-BII equilibrium inducing a global dynamic curvature of the duplex. J Mol Biol. 1998; 279(1):127-42. DOI: 10.1006/jmbi.1998.1757. View

Sims G, Kim S . Global mapping of nucleic acid conformational space: dinucleoside monophosphate conformations and transition pathways among conformational classes. Nucleic Acids Res. 2003; 31(19):5607-16. PMC: 206451. DOI: 10.1093/nar/gkg750. View

Lilley D . Structures of helical junctions in nucleic acids. Q Rev Biophys. 2000; 33(2):109-59. DOI: 10.1017/s0033583500003590. View

Smith F, Feigon J . Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature. 1992; 356(6365):164-8. DOI: 10.1038/356164a0. View

Murphy 4th F, Churchill M . Nonsequence-specific DNA recognition: a structural perspective. Structure. 2000; 8(4):R83-9. DOI: 10.1016/s0969-2126(00)00126-x. View

Pelletier H, Sawaya M, Kumar A, Wilson S, KRAUT J . Structures of ternary complexes of rat DNA polymerase beta, a DNA template-primer, and ddCTP. Science. 1994; 264(5167):1891-903. View

Drew H, Wing R, Takano T, Broka C, Tanaka S, Itakura K . Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci U S A. 1981; 78(4):2179-83. PMC: 319307. DOI: 10.1073/pnas.78.4.2179. View

10.

Neidle S . The structures of quadruplex nucleic acids and their drug complexes. Curr Opin Struct Biol. 2009; 19(3):239-50. DOI: 10.1016/j.sbi.2009.04.001. View

11.

Hunter C, Lu X . DNA base-stacking interactions: a comparison of theoretical calculations with oligonucleotide X-ray crystal structures. J Mol Biol. 1997; 265(5):603-19. DOI: 10.1006/jmbi.1996.0755. View

12.

Tolstorukov M, Jernigan R, Zhurkin V . Protein-DNA hydrophobic recognition in the minor groove is facilitated by sugar switching. J Mol Biol. 2004; 337(1):65-76. DOI: 10.1016/j.jmb.2004.01.011. View

13.

Gill M, Strobel S, Loria J . Crystallization and characterization of the thallium form of the Oxytricha nova G-quadruplex. Nucleic Acids Res. 2006; 34(16):4506-14. PMC: 1636370. DOI: 10.1093/nar/gkl616. View

14.

Packer M, Hunter C . Sequence-dependent DNA structure: the role of the sugar-phosphate backbone. J Mol Biol. 1998; 280(3):407-20. DOI: 10.1006/jmbi.1998.1865. View

15.

Heddi B, Foloppe N, Bouchemal N, Hantz E, Hartmann B . Quantification of DNA BI/BII backbone states in solution. Implications for DNA overall structure and recognition. J Am Chem Soc. 2006; 128(28):9170-7. DOI: 10.1021/ja061686j. View

16.

Robinson H, Gao Y, McCrary B, Edmondson S, Shriver J, Wang A . The hyperthermophile chromosomal protein Sac7d sharply kinks DNA. Nature. 1998; 392(6672):202-5. DOI: 10.1038/32455. View

17.

Doublie S, Tabor S, Long A, Richardson C, Ellenberger T . Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution. Nature. 1998; 391(6664):251-8. DOI: 10.1038/34593. View

18.

Drew H, DICKERSON R . Structure of a B-DNA dodecamer. III. Geometry of hydration. J Mol Biol. 1981; 151(3):535-56. DOI: 10.1016/0022-2836(81)90009-7. View

19.

Berman H, Olson W, Beveridge D, Westbrook J, Gelbin A, Demeny T . The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids. Biophys J. 1992; 63(3):751-9. PMC: 1262208. DOI: 10.1016/S0006-3495(92)81649-1. View

20.

Choo Y, Klug A . Physical basis of a protein-DNA recognition code. Curr Opin Struct Biol. 1997; 7(1):117-25. DOI: 10.1016/s0959-440x(97)80015-2. View