scholarly journals Archaeal chromatin ‘slinkies’ are inherently dynamic complexes with deflected DNA wrapping pathways

2020 ◽  
Author(s):  
Samuel Bowerman ◽  
Jeff Wereszczynski ◽  
Karolin Luger
Keyword(s):  
Molecular Dynamics ◽  
Analytical Ultracentrifugation ◽  
Base Pairs ◽  
Solution Structures ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Out Of Plane ◽  
Crystal Contacts ◽  
Chromatin Packing ◽  
Dynamics Simulations

AbstractEukaryotes and many archaea package their DNA with histones. While the four eukaryotic histones wrap ∼147 DNA base pairs into nucleosomes, archaeal histones form “nucleosome-like” complexes that continuously wind between 60 - 500 base pairs of DNA (“archaeasomes”), suggested by crystal contacts and analysis of cellular chromatin. Solution structures of large archaeasomes (>90 DNA base pairs) have never been directly observed. Here, we utilize molecular dynamics simulations, analytical ultracentrifugation, and cryoEM to structurally characterize the solution state of archaeasomes on longer DNA. Simulations reveal dynamics of increased accessibility without disruption of DNA-binding or tetramerization interfaces. Mg2+ concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90° out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility.

scholarly journals Archaeal chromatin ‘slinkies’ are inherently dynamic complexes with deflected DNA wrapping pathways

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Samuel Bowerman ◽  
Jeff Wereszczynski ◽  
Karolin Luger
Keyword(s):  
Molecular Dynamics ◽  
Analytical Ultracentrifugation ◽  
Base Pairs ◽  
Solution Structures ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Out Of Plane ◽  
Crystal Contacts ◽  
Chromatin Packing ◽  
Dynamics Simulations

Eukaryotes and many archaea package their DNA with histones. While the four eukaryotic histones wrap ~147 DNA base pairs into nucleosomes, archaeal histones form ‘nucleosome-like’ complexes that continuously wind between 60 and 500 base pairs of DNA (‘archaeasomes’), suggested by crystal contacts and analysis of cellular chromatin. Solution structures of large archaeasomes (>90 DNA base pairs) have never been directly observed. Here, we utilize molecular dynamics simulations, analytical ultracentrifugation, and cryoEM to structurally characterize the solution state of archaeasomes on longer DNA. Simulations reveal dynamics of increased accessibility without disruption of DNA-binding or tetramerization interfaces. Mg2+ concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90o out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility.

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

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).

New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

2020 ◽  
Vol 17 (2) ◽  
pp. 124-137 ◽  
Author(s):  
Adel Mahmoud Attia ◽  
Ahmed Ibrahin Khodair ◽  
Eman Abdelnasser Gendy ◽  
Mohammed Abu El-Magd ◽  
Yaseen Ali Mosa Mohamed Elshaier
Keyword(s):  
Dna Damage ◽  
Anticancer Agents ◽  
Active Compound ◽  
Docking Study ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Antiviral Activities ◽  
Active Methylene ◽  
Damage Study

Background:Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.Objective:The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.Methods:A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.Results:The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.Conclusion:Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

On the change of the order od stability of DNA base pairs as a result of the methylation of guanine

1988 ◽  
Vol 53 (9) ◽  
pp. 1943-1945
Author(s):  
Pavel Hobza ◽  
Camille Sandorfy
Keyword(s):  
Ab Initio ◽  
Base Pairs ◽  
Dispersion Energy ◽  
Dna Base ◽  
Dna Base Pairs

The interaction of the 6-O methylguanine cation with cytosine and thymine was studied using the ab initio SCF method in combination with a London type expression for dispersion energy. The structure of the complex formed with cytosine differs from that found previously with guanine itself.

scholarly journals Elucidating Solution Structures of Cyclic Peptides Using Molecular Dynamics Simulations

2021 ◽  
Vol 121 (4) ◽  
pp. 2292-2324
Author(s):  
Jovan Damjanovic ◽  
Jiayuan Miao ◽  
He Huang ◽  
Yu-Shan Lin
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Cyclic Peptides ◽  
Solution Structures ◽  
Dynamics Simulations

scholarly journals RNA Delivery via DNA-Inspired Janus Base Nanotubes for Extracellular Matrix Penetration

MRS Advances ◽  
2020 ◽  
Vol 5 (16) ◽  
pp. 815-823
Author(s):  
Ian Sands ◽  
Jinhyung Lee ◽  
Wuxia Zhang ◽  
Yupeng Chen
Keyword(s):  
Extracellular Matrix ◽  
Small Rnas ◽  
Base Pairs ◽  
Major Barrier ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Negative Surface ◽  
Negative Surface Charge ◽  
Delivery Vehicles ◽  
Low Cell Density

AbstractRNA delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for RNA delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with small RNAs to form nano-rod delivery vehicles (termed as “Nanopieces”). Nanopieces have a diameter of ∼20nm (smallest delivery vehicles after cargo loading) and a length of ∼100nm. They present a novel breakthrough in ECM penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration.

scholarly journals UV-induced hydrogen transfer in DNA base pairs promoted by dark nπ* states

2020 ◽  
Vol 56 (2) ◽  
pp. 201-204 ◽  
Author(s):  
Kinga E. Szkaradek ◽  
Petr Stadlbauer ◽  
Jiří Šponer ◽  
Robert W. Góra ◽  
Rafał Szabla
Keyword(s):  
Excited State ◽  
Hydrogen Transfer ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs

Formation of an excited-state complex enables ultrafast photorelaxation of dark nπ* states in GC and HC base pairs.

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