Pyrenemethyl ara-Uridine-2′-carbamate: A Strong Interstrand Excimer in the Major Groove of a DNA Duplex

ChemBioChem ◽  
2003 ◽  
Vol 4 (9) ◽  
pp. 841-847 ◽  
Author(s):  
Natalia N. Dioubankova ◽  
Andrei D. Malakhov ◽  
Dmitry A. Stetsenko ◽  
Michael J. Gait ◽  
Pavel E. Volynsky ◽  
...  
Keyword(s):  
Major Groove ◽  
Dna Duplex

Investigation of changes in the arrangement of water molecules and salt ions surrounding different atoms of the DNA molecule during the melting process: a molecular dynamics simulation study

2015 ◽  
Vol 93 (3) ◽  
pp. 348-361 ◽  
Author(s):  
C. Izanloo
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Double Helix ◽  
Melting Process ◽  
Minor Groove ◽  
Dynamics Simulation ◽  
Transition Curve ◽  
Water Molecules ◽  
Major Groove ◽  
Dna Duplex

A molecular dynamics simulation was performed on a B-DNA duplex (CGCGAATTGCGC) at different temperatures. The DNA was immerged in a saltwater medium with 1 mol/L NaCl concentration. The arrangements of water molecules and cations around the different atoms of DNA on the melting pathway were investigated. Almost for all atoms of the DNA by double helix → single-stranded transition, the water molecules released from the DNA duplex and cations were close to single-stranded DNA, but this behavior was not clearly seen at melting temperatures. Therefore, release of water molecules and cations approaching the DNA by the increase of temperature does not have any effect on the sharpness of the transition curve. Most of the water molecules and cations were found to be around the negatively charged phosphate oxygen atoms. The number of water molecules released from the first shell hydration upon melting in the minor groove was higher than in the major groove, and intrusion of cations into the minor groove after melting was higher than into the major groove. The hydrations of imino protons were different from each other and were dependent on DNA bases.

Double-Coding Nucleic Acids: Introduction of a Nucleobase Sequence in the Major Groove of the DNA Duplex Using Double-Headed Nucleotides

2014 ◽  
Vol 79 (17) ◽  
pp. 8020-8030 ◽  
Author(s):  
Pawan Kumar ◽  
Antoni Figueras Sorinas ◽  
Lise J. Nielsen ◽  
Maria Slot ◽  
Kirstine Skytte ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Major Groove ◽  
Dna Duplex

scholarly journals Dissociation pathways of the p53 DNA binding domain from DNA and critical roles of key residues elucidated by dPaCS-MD/MSM

2021 ◽  
Author(s):  
Mohamed Sobeh ◽  
Akio kitao
Keyword(s):  
Free Energy ◽  
Dna Binding ◽  
Energy Landscape ◽  
Minor Groove ◽  
Binding Domain ◽  
Free Energy Landscape ◽  
Dna Binding Domain ◽  
Major Groove ◽  
Dna Duplex ◽  
Key Residues

The dissociation process of the DNA binding domain of p53 (p53-DBD) from a DNA duplex that contains the consensus sequence, which is the specific target of p53-DBD, was investigated by a combination of dissociation parallel cascade selection molecular dynamics (dPaCS-MD) and the Markov state model (MSM). Based on an all-atom model including explicit solvent, we first simulated the p53-DBD dissociation processes by 75 trials of dPaCS-MD, which required an average simulation time of 11.2 ± 2.2 ns per trial. By setting the axis of the DNA duplex as the Z-axis and the binding side of p53-DBD on DNA as the + side of the X-axis, we found that dissociations took place along the +X and −Y directions (−Y directions) in 93% of the cases, while 7% of the cases moved along +X and +Y directions (+Y directions). Toward the −Y directions, p53-DBD dissociated first from the major groove and then detached from the minor groove, while unbinding from the minor groove occurred first in dissociations along the +Y directions. Analysis of the free energy landscape by MSM showed that loss of the minor groove interaction with p53-DBD toward the +Y directions incurred a relatively high energy cost (1.1 kcal/mol) upon a critical transition, whereas major groove detachment more frequently occurred with lower free energy costs. The standard binding free energy calculated from the free energy landscape was −10.9 ± 0.4 kcal/mol, which agrees with an experimental value of –11.1 kcal/mol. These results indicate that the dPaCS-MD/MSM combination can be a powerful tool to investigate dissociation mechanisms of two large molecules. Minor groove binding is mainly stabilized by R248, identified as the most important residue that tightly binds deep inside the minor groove. Analysis of the p53 key residues for DNA binding indicates high correlations with cancer-related mutations, confirming that impairment of the interactions between p53-DBD and DNA can be frequently related to cancer.

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