Structure and stability of a model pyrimidine-purine-purine DNA triple helix with a GC·T mismatch by simulation

S. Weerasinghe, P. E. Smith, Bernard Pettitt

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

A 1.5 ns long molecular dynamics simulation was conducted to compare the structure and stability of a model DNA triplex in saline solution with that found from experiments. The model DNA was an antiparallel py·pu·pu (CG·G) 7-mer structure which contained a GC·T mismatch triplet at the middle of the sequence. The local conformation of the mismatch triplet and the effects of this triplet on the global helical structure suggest that the GC·T triplet forms stable hydrogen bonds and shows distortions from an in-plane alignment. The overall rms deviation of the triplex is similar to one without a mismatch, although the thymine base in the mismatch triplet shows significantly higher mobility. A high coordination probability for water between the G and T bases in the mismatch triplet was observed to have an effect on the stability of non-hydrogen-bonded base pairs. Average helical parameters, sugar pucker, and backbone dihedral angles indicate that the CG·G triplets on the 3' side of the mismatch triplet possess different structural and dynamical properties than that of the 5' side. These observations are consistent with recently available experimental results and provide an interpretation of the observed experimental structure. They also suggest that inclusion of explicit water molecules is necessary in order to understand and predict the interaction between the third strand and duplex DNA.

Original languageEnglish (US)
Pages (from-to)16269-16278
Number of pages10
JournalBiochemistry
Volume34
Issue number50
DOIs
StatePublished - 1995
Externally publishedYes

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Thymine
Water
DNA
Dihedral angle
Molecular Dynamics Simulation
Sodium Chloride
Sugars
Base Pairing
Conformations
Molecular dynamics
Hydrogen
Hydrogen bonds
Molecules
Computer simulation
Experiments
purine
pyrimidine
triplex DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structure and stability of a model pyrimidine-purine-purine DNA triple helix with a GC·T mismatch by simulation. / Weerasinghe, S.; Smith, P. E.; Pettitt, Bernard.

In: Biochemistry, Vol. 34, No. 50, 1995, p. 16269-16278.

Research output: Contribution to journalArticle

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AB - A 1.5 ns long molecular dynamics simulation was conducted to compare the structure and stability of a model DNA triplex in saline solution with that found from experiments. The model DNA was an antiparallel py·pu·pu (CG·G) 7-mer structure which contained a GC·T mismatch triplet at the middle of the sequence. The local conformation of the mismatch triplet and the effects of this triplet on the global helical structure suggest that the GC·T triplet forms stable hydrogen bonds and shows distortions from an in-plane alignment. The overall rms deviation of the triplex is similar to one without a mismatch, although the thymine base in the mismatch triplet shows significantly higher mobility. A high coordination probability for water between the G and T bases in the mismatch triplet was observed to have an effect on the stability of non-hydrogen-bonded base pairs. Average helical parameters, sugar pucker, and backbone dihedral angles indicate that the CG·G triplets on the 3' side of the mismatch triplet possess different structural and dynamical properties than that of the 5' side. These observations are consistent with recently available experimental results and provide an interpretation of the observed experimental structure. They also suggest that inclusion of explicit water molecules is necessary in order to understand and predict the interaction between the third strand and duplex DNA.

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