Structure–activity relationships of a caged thrombin binding DNA aptamer: Insight gained from molecular dynamics simulation studies

Jayapal, Prabha; Mayer, Günter; Heckel, Alexander; Wennmohs, Frank

doi:10.1016/j.jsb.2009.01.010

Cited by 30 publications

(28 citation statements)

References 63 publications

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“…The lateral loops of 15-TBA are represented well in the parm98 force field though the short simulation time scale precludes definitive conclusions. In a simulation published by Jayapal et al, 28 predistorted 15-TBA recovers a structure similar to ray-based model. Two G-quartets, upper (G1, G6, G10, G15) and lower (G2, G5, G11, G14), form G-quadruplex.…”

Section: Introductionmentioning

confidence: 67%

Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations

Reshetnikov

Golovin

Спиридонова

et al. 2010

J. Chem. Theory Comput.

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The thrombin-binding aptamer (15-TBA) is a 15-mer DNA oligonucleotide with sequence d(GGTTGGTGTGGTTGG). 15-TBA folds into a quadruplex DNA (G-DNA) structure with two planar G-quartets connected by three single-stranded loops. The arrangement of the 15-TBA-thrombin complex is unclear, particularly with respect to the precise 15-TBA residues that interact with the thrombin structure. Our present understanding suggests either the 15-TBA single stranded loops containing sequential thymidines (TT) or alternatively a single-stranded loop, containing a guanine flanked by 2 thymidines (TGT), physically associates with thrombin protein. In the present study, the explicit solvent molecular dynamics (MD) simulation method was utilized to further analyze the 15-TBA-thrombin three-dimensional structure. Functional annotation of the loop residues was made with long simulations in the parmbsc0 force field. In total, the elapsed time of simulations carried out in this study exceeds 12 microseconds, substantially surpassing previous G-DNA simulation reports. Our simulations suggest that the TGT-loop function is to stabilize the structure of the aptamer, while the TT-loops participate in direct binding to thrombin. The findings of the present report advance our understanding of the molecular structure of the 15-TBA-thrombin structure further enabling the construction of biosensors for aptamer bases and the development of anticoagulant agents.

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Section: Introductionmentioning

confidence: 67%

Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations

Reshetnikov

Golovin

Спиридонова

et al. 2010

J. Chem. Theory Comput.

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“…Within the quadruplex structure, the quartets are located one above the other; a minimum of two quartets are required for the structural stability of the tetraplex [21]. The number of guanines in each individual G-block is directly related to the number of G-tetrads in the final folded quadruplex.…”

Section: Introductionmentioning

confidence: 99%

Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

2010

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The present work is devoted to the analysis of the G-quadruplex DNA structure using the bioinformatics method. The interest towards quadruplex DNAs is determined by their involvement in the functioning of telomeres and onco-promoters as well as by the possibility to create on their basis aptamers and nanostructures. Here, we present an algorithm for a general analysis of the polymorphism of the G-quadruplex structure from the data bank PDB using original parameters. 74 structures were grouped according to the following parameters: the number of DNA strands, the number of G-quartets, and the location and orientation of the connecting loops. Two quantitative parameters were used to describe the quadruplex structure: the twist angle between two adjacent quartets (analogous to that for the complementary pair in the duplex DNA) and the quartet planarity (an original parameter). The distribution patterns of these values are specific for each group of quadruplex structures and are dependent upon the type of connecting loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel quadruplex was used as a comparison template. The lateral loops introduce the strongest distortion into the structure of quadruplexes: the values of the twist angles are the lowest and are not typical for the other quadruplex groups. The loops of the diagonal type introduce much weaker deformation into quadruplexes; the structures with propeller loops are characterized by the optimum geometry of G-quartets. Hence, the correlation between the twist angle and the tension in the structure of quadruplex DNA is revealed.

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“…One computational modeling technique applicable for the analysis of bio molecular motion and interactions is based on Molecular Dynamics (MD) modeling [6], [7]. This modeling methodology has been recently applied to determine the chemical, physical and mechanical properties of materials.…”

Section: A Molecular Dynamics Modelingmentioning

confidence: 99%

Computational Modeling of Peptide – Aptamer Binding in Biosensor Applications

Rhinehardt¹,

Mohan²,

Srinivas³

et al. 2013

IJBBB

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Structure–activity relationships of a caged thrombin binding DNA aptamer: Insight gained from molecular dynamics simulation studies

Cited by 30 publications

References 63 publications

Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations

Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations

Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

Computational Modeling of Peptide – Aptamer Binding in Biosensor Applications

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