Minor Groove Deformability of DNA: A Molecular Dynamics Free Energy Simulation Study

Zacharias, Martin

doi:10.1529/biophysj.106.083816

Cited by 45 publications

(30 citation statements)

References 62 publications

(97 reference statements)

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“…This agrees with earlier simulations using the parm94 force field (26,47). For bending up to 150°, the free energy cost is 12 kcal mol −1 for [GC] and [Atract-2] and 10 kcal mol −1 for [Atract-1].…”

Section: Discussionsupporting

confidence: 92%

Local and global effects of strong DNA bending induced during molecular dynamics simulations

Curuksu¹,

Zacharias²,

Lavery³

et al. 2009

Nucleic Acids Research

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DNA bending plays an important role in many biological processes, but its molecular and energetic details as a function of base sequence remain to be fully understood. Using a recently developed restraint, we have studied the controlled bending of four different B-DNA oligomers using molecular dynamics simulations. Umbrella sampling with the AMBER program and the recent parmbsc0 force field yield free energy curves for bending. Bending 15-base pair oligomers by 90° requires roughly 5 kcal mol−1, while reaching 150° requires of the order of 12 kcal mol−1. Moderate bending occurs mainly through coupled base pair step rolls. Strong bending generally leads to local kinks. The kinks we observe all involve two consecutive base pair steps, with disruption of the central base pair (termed Type II kinks in earlier work). A detailed analysis of each oligomer shows that the free energy of bending only varies quadratically with the bending angle for moderate bending. Beyond this point, in agreement with recent experiments, the variation becomes linear. An harmonic analysis of each base step yields force constants that not only vary with sequence, but also with the degree of bending. Both these observations suggest that DNA is mechanically more complex than simple elastic rod models would imply.

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Section: Discussionsupporting

confidence: 92%

Local and global effects of strong DNA bending induced during molecular dynamics simulations

Curuksu¹,

Zacharias²,

Lavery³

et al. 2009

Nucleic Acids Research

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“…The permanent atomic movement around single bonds in DNA may be represented as coupling of S↔N interconversion in a sugar ring [39–42], epsilon/dzeta changes (BI↔BII motion) [43–46], alfa/gamma flips [47, 48] and mutual rotation of sugar around the glycoside bond [49]. NMR data show that positions of N↔S equilibrium and BI↔BII equilibrium are interdependent and that the dynamics of conformational changes occur on the picosecond to nanosecond timescale [50].…”

Section: Resultsmentioning

confidence: 99%

Structural features of DNA that determine RNA polymerase II core promoter

et al. 2016

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BackgroundThe general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common characteristics of DNA region that define it as a promoter for the RNA polymerase II (Pol II).ResultsThe profiles of a large number of physical and structural characteristics, averaged over representative sets of the Pol II minimal core promoters of the evolutionary divergent species from animals, plants and unicellular fungi were analysed. In addition to the characteristics defined at the base-pair steps, we, for the first time, use profiles of the ultrasonic cleavage and DNase I cleavage indexes, informative for internal properties of each complementary strand.ConclusionsDNA of the core promoters of metazoans and Schizosaccharomyces pombe has similar structural organization. Its mechanical and 3D structural characteristics have singular properties at the positions of TATA-box. The minor groove is broadened and conformational motion is decreased in that region. Special characteristics of conformational behavior are revealed in metazoans at the region, which connects the end of TATA-box and the transcription start site (TSS). The intensities of conformational motions in the complementary strands are periodically changed in opposite phases. They are noticeable, best of all, in mammals. Such conformational features are lacking in the core promoters of S. pombe. The profiles of Saccharomyces cerevisiae core promoters significantly differ: their singular region is shifted down thus pointing to the uniqueness of their structural organization. Obtained results may be useful in genetic engineering for artificial modulation of the promoter strength.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3292-z) contains supplementary material, which is available to authorized users.

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“…Also, several other DNA binding proteins bind to the minor groove of DNA, which often results in change in conformation of the minor groove (8), namely its opening and greater accessibility (9). Among these are the high mobility group (HMG) proteins, HMG-D (PDB ID code 1QRV), lymphoid enhancer factor (LEF-1) (PDB ID code 2LEF), and the male sex determining factor SRY (PDB ID code 1J46).…”

Section: ⌬N11-d13k-c3mentioning

confidence: 99%

Structure of a protein–DNA complex essential for DNA protection in spores of Bacillus species

Lee¹,

Bumbaca²,

Kosman

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

105

121

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The DNA-binding ␣/␤-type small acid-soluble proteins (SASPs) are a major factor in the resistance and long-term survival of spores of Bacillus species by protecting spore DNA against damage due to desiccation, heat, toxic chemicals, enzymes, and UV radiation. We now report the crystal structure at 2.1 Å resolution of an ␣/␤-type SASP bound to a 10-bp DNA duplex. In the complex, the ␣/␤-type SASP adopt a helix-turn-helix motif, interact with DNA through minor groove contacts, bind to Ϸ6 bp of DNA as a dimer, and the DNA is in an A-B type conformation. The structure of the complex provides important insights into the molecular details of both DNA and ␣/␤-type SASP protection in the complex and thus also in spores.␣/␤-type SASP ͉ A-type DNA ͉ DNA damage ͉ molecular modeling ͉ spore resistance S pores of Bacillus and Clostridium species are extremely resistant to desiccation, heat, toxic chemicals, enzymes, and radiation. This high resistance is the major reason that spores of some species are agents of food spoilage and food poisoning and that B. anthracis spores are a biological weapon. Spore resistance is due to many factors, a major one being the protection of spore DNA against damage by the binding of small, acid-soluble proteins (SASPs) of the ␣/␤-type (1, 2). These 59-75 residue proteins: (i) are encoded by multiple genes, (ii) comprise a protein family whose amino acid sequences are very highly conserved within and between species, (iii) are nonspecific DNA-binding proteins with apparent binding constants for random sequence DNA of 15-100 mM, (iv) are synthesized only within the developing forespore during sporulation; and (v) comprise 3-5% of total spore protein. The high levels of ␣/␤-type SASPs in spores are sufficient to saturate the spore DNA, and the DNA within this nucleoprotein complex is protected from a variety of environmental insults. Indeed, the binding of ␣/␤-type SASPs provides primary protection of spore DNA against damage by desiccation, heat, many genotoxic chemicals, enzymes, and UV radiation (1,3).In this study, we used x-ray crystallography to determine a 2.1 Å resolution structure of a complex between a 10-bp DNA duplex and an engineered ␣/␤-type SASP originally obtained from B. subtilis. Analysis of this crystal structure provides important insight into the molecular mechanisms underlying the protection of both the protein and DNA components of the complex and the molecular details of their interactions. These results explain a great deal about the extreme resistance of the DNA in bacterial spores and thus explain much of bacterial spore resistance in atomic detail. Results and DiscussionOverall Structure and Protection of the Protein in the Complex. The ␣/␤-type SASP chosen to form the complex with DNA for crystallization was B. subtilis SspC ⌬N11-D13K-C3, a 64-aa derivative engineered to bind tightly to DNA (4), which was an oligo(dG)⅐oligo(dC) 10-mer with single 3Ј-dA overhangs (5) The preparation and crystallization of the protein-DNA complex are described in ref. 6, and the struct...

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Minor Groove Deformability of DNA: A Molecular Dynamics Free Energy Simulation Study

Cited by 45 publications

References 62 publications

Local and global effects of strong DNA bending induced during molecular dynamics simulations

Local and global effects of strong DNA bending induced during molecular dynamics simulations

Structural features of DNA that determine RNA polymerase II core promoter

Structure of a protein–DNA complex essential for DNA protection in spores of Bacillus species

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