Photoinduced Azobenzene-modified DNA Dehybridization: Insights into Local and Cooperativity Effects from a Molecular Dynamics Study

Abstract The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy ($$\Delta G_{{37}}^{^\circ }$$ ) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the $$\Delta G_{{37}}^{^\circ }$$ of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

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Can modified DNA base pairs with chalcogen bonding expand the genetic alphabet? A combined quantum chemical and molecular dynamics simulation study

Physical Chemistry Chemical Physics ◽

10.1039/d0cp04921b ◽

2020 ◽

Vol 22 (41) ◽

pp. 23754-23765

Author(s):

Karan Deep Sharma ◽

Preetleen Kathuria ◽

Stacey D. Wetmore ◽

Purshotam Sharma

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Hydrogen Bonds ◽

Quantum Chemical ◽

Computational Study ◽

Dynamics Simulation ◽

Base Pairs ◽

Dna Base ◽

Modified Dna ◽

Dna Base Pairs

A comprehesive computational study is presented with the goal to design and analyze model chalcogen-bonded modified nucleobase pairs that replace one or two Watson–Crick hydrogen bonds of the canonical A:T or G:C pair with chalcogen bond(s).

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Molecular-Dynamics Simulations of Insertion of Chemically Modified DNA Nanostructures into a Water-Chloroform Interface

Biophysical Journal ◽

10.1529/biophysj.107.119230 ◽

2008 ◽

Vol 95 (3) ◽

pp. 1099-1107 ◽

Cited By ~ 4

Author(s):

Jianping Lin ◽

Nadrian C. Seeman ◽

Nagarajan Vaidehi

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Dna Nanostructures ◽

Chemically Modified ◽

Modified Dna ◽

Dynamics Simulations

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Structural characterization of an N-acetyl-2-aminofluorene (AAF) modified DNA oligomer by NMR, energy minimization, and molecular dynamics

Biochemistry ◽

10.1021/bi00061a005 ◽

1993 ◽

Vol 32 (10) ◽

pp. 2481-2497 ◽

Cited By ~ 77

Author(s):

Suzanne F. O'Handley ◽

David G. Sanford ◽

Rong Xu ◽

Cathy C. Lester ◽

Brian E. Hingerty ◽

...

Keyword(s):

Molecular Dynamics ◽

Structural Characterization ◽

Energy Minimization ◽

Modified Dna

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Molecular Dynamics Study of DNA Duplex Containing Carbazole-Derived Universal Base

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.506.258 ◽

2012 ◽

Vol 506 ◽

pp. 258-261

Author(s):

W. Soodsawang ◽

T. Benchawan ◽

U. Wichai ◽

Y. Tantirungrotechai

Keyword(s):

Molecular Dynamics ◽

Md Simulations ◽

Reference Sequence ◽

Dna Duplexes ◽

Structure And Dynamics ◽

Duplex Stability ◽

Stability Order ◽

The Stability ◽

Duplex Formation ◽

Universal Bases

Universal base is a man-made residue that can be incorporated into the DNA double strands without any discrimination against natural bases (A, C, G, T). The MD simulations with AMBER99 force field were employed to investigate the structure and dynamics of the modified 15-mer DNA duplexes containing carbazole-derived universal bases: carbazole (CBZ), 3,6-dicyanocarbazole (DCC), 3,6-dinitrocarbazole (DNC), and 3-nitro-6-cyanocarbazole (NCC), where X = CBZ, DCC, DNC, or NCC, respectively. The RMSD and B-factor of the modified DNAs backbones around the universal base unit fluctuate more than the reference sequence in the same position. The thermodynamic parameter for duplex stability was estimated by using MM-PBSA method. The averaged duplex formation free energy (ΔG) of all modified DNAs exhibited that the stability order was approximately DNC>NCC>CBZ>DCC, which differed from the reference sequence exceptional DNC unit. The averaged ΔG value of the DNC unit is very close to that of the reference sequence. This calculation indicated that the DNC unit can be considered as a good candidate for using as a universal base.

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Controlling aggregation of cholesterol-modified DNA nanostructures

Nucleic Acids Research ◽

10.1093/nar/gkz914 ◽

2019 ◽

Vol 47 (21) ◽

pp. 11441-11451 ◽

Cited By ~ 7

Author(s):

Alexander Ohmann ◽

Kerstin Göpfrich ◽

Himanshu Joshi ◽

Rebecca F Thompson ◽

Diana Sobota ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Lipid Membranes ◽

Structural Control ◽

Polyacrylamide Gel Electrophoresis ◽

Dna Nanotechnology ◽

Dna Nanostructures ◽

Hydrophobic Moiety ◽

Modified Dna ◽

Dynamics Simulations

Abstract DNA nanotechnology allows for the design of programmable DNA-built nanodevices which controllably interact with biological membranes and even mimic the function of natural membrane proteins. Hydrophobic modifications, covalently linked to the DNA, are essential for targeted interfacing of DNA nanostructures with lipid membranes. However, these hydrophobic tags typically induce undesired aggregation eliminating structural control, the primary advantage of DNA nanotechnology. Here, we study the aggregation of cholesterol-modified DNA nanostructures using a combined approach of non-denaturing polyacrylamide gel electrophoresis, dynamic light scattering, confocal microscopy and atomistic molecular dynamics simulations. We show that the aggregation of cholesterol-tagged ssDNA is sequence-dependent, while for assembled DNA constructs, the number and position of the cholesterol tags are the dominating factors. Molecular dynamics simulations of cholesterol-modified ssDNA reveal that the nucleotides wrap around the hydrophobic moiety, shielding it from the environment. Utilizing this behavior, we demonstrate experimentally that the aggregation of cholesterol-modified DNA nanostructures can be controlled by the length of ssDNA overhangs positioned adjacent to the cholesterol. Our easy-to-implement method for tuning cholesterol-mediated aggregation allows for increased control and a closer structure–function relationship of membrane-interfacing DNA constructs — a fundamental prerequisite for employing DNA nanodevices in research and biomedicine.

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