Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA

2014 ◽  
Vol 10 (8) ◽  
pp. 3177-3189 ◽  
Author(s):  
Marie Zgarbová ◽  
Michal Otyepka ◽  
Jiří Šponer ◽  
Filip Lankaš ◽  
Petr Jurečka
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Base Pair ◽  
Dna And Rna ◽  
Dynamics Simulations

scholarly journals Same fold, different properties: polarizable molecular dynamics simulations of telomeric and TERRA G-quadruplexes

2019 ◽  
Vol 48 (2) ◽  
pp. 561-575 ◽  
Author(s):  
Justin A Lemkul
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Dipole Moments ◽  
Sequence Motifs ◽  
Telomeric Dna ◽  
Rna Sequences ◽  
Dna And Rna ◽  
Induced Dipole ◽  
Dynamics Simulations

Abstract DNA and RNA sequences rich in guanine can fold into noncanonical structures called G-quadruplexes (GQs), which exhibit a common stem structure of Hoogsteen hydrogen-bonded guanine tetrads and diverse loop structures. GQ sequence motifs are overrepresented in promoters, origins of replication, telomeres, and untranslated regions in mRNA, suggesting roles in modulating gene expression and preserving genomic integrity. Given these roles and unique aspects of different structures, GQs are attractive targets for drug design, but greater insight into GQ folding pathways and the interactions stabilizing them is required. Here, we performed molecular dynamics simulations to study two bimolecular GQs, a telomeric DNA GQ and the analogous telomeric repeat-containing RNA (TERRA) GQ. We applied the Drude polarizable force field, which we show outperforms the additive CHARMM36 force field in both ion retention and maintenance of the GQ folds. The polarizable simulations reveal that the GQs bind bulk K+ ions differently, and that the TERRA GQ accumulates more K+ ions, suggesting different ion interactions stabilize these structures. Nucleobase dipole moments vary as a function of position and also contribute to ion binding. Finally, we show that the TERRA GQ is more sensitive than the telomeric DNA GQ to water-mediated modulation of ion-induced dipole-dipole interactions.

DNA Base Pair Hybridization and Water-Mediated Metastable Structures Studied by Molecular Dynamics Simulations

Biochemistry ◽  
2011 ◽  
Vol 50 (44) ◽  
pp. 9628-9632 ◽  
Author(s):  
Wenpeng Qi ◽  
Bo Song ◽  
Xiaoling Lei ◽  
Chunlei Wang ◽  
Haiping Fang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Base Pair ◽  
Metastable Structures ◽  
Dna Base ◽  
Dna Base Pair ◽  
Dynamics Simulations

scholarly journals Ethidium bromide interactions with DNA: an exploration of a classic DNA–ligand complex with unbiased molecular dynamics simulations

2021 ◽  
Vol 49 (7) ◽  
pp. 3735-3747
Author(s):  
Rodrigo Galindo-Murillo ◽  
Thomas E Cheatham
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Ethidium Bromide ◽  
Base Pair ◽  
Force Fields ◽  
Ligand Complex ◽  
Base Pairs ◽  
Duplex System ◽  
Double Stranded Dna ◽  
Dynamics Simulations

Abstract Visualization of double stranded DNA in gels with the binding of the fluorescent dye ethidium bromide has been a basic experimental technique in any molecular biology laboratory for >40 years. The interaction between ethidium and double stranded DNA has been observed to be an intercalation between base pairs with strong experimental evidence. This presents a unique opportunity for computational chemistry and biomolecular simulation techniques to benchmark and assess their models in order to see if the theory can reproduce experiments and ultimately provide new insights. We present molecular dynamics simulations of the interaction of ethidium with two different double stranded DNA models. The first model system is the classic sequence d(CGCGAATTCGCG)2 also known as the Drew–Dickerson dodecamer. We found that the ethidium ligand binds mainly stacked on, or intercalated between, the terminal base pairs of the DNA with little to no interaction with the inner base pairs. As the intercalation at the terminal CpG steps is relatively rapid, the resultant DNA unwinding, rigidification, and increased stability of the internal base pair steps inhibits further intercalation. In order to reduce these interactions and to provide a larger groove space, a second 18-mer DNA duplex system with the sequence d(GCATGAACGAACGAACGC) was tested. We computed molecular dynamics simulations for 20 independent replicas with this sequence, each with ∼27 μs of sampling time. Results show several spontaneous intercalation and base-pair eversion events that are consistent with experimental observations. The present work suggests that extended MD simulations with modern DNA force fields and optimized simulation codes are allowing the ability to reproduce unbiased intercalation events that we were not able to previously reach due to limits in computing power and the lack of extensively tested force fields and analysis tools.

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