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16:24
Analyzing and Building Nucleic Acid Structures with 3DNA
Published on: April 26, 2013
A computational study of expanded heterocyclic nucleosides in DNA
Peter I O'Daniel1, Malcolm Jefferson, Olaf Wiest
1Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.
Journal of Biomolecular Structure & Dynamics
|September 24, 2008
Summary
This study explored DNA bases with added furan, pyrrole, or thiophene rings. These modifications altered DNA structure, increasing major groove width and favoring base stacking over pairing.
Area of Science:
- Biochemistry
- Molecular Biology
- Computational Chemistry
Background:
- DNA structure and function are critical for genetic processes.
- Modifying nucleobase structures can alter DNA helix properties.
- Heterocyclic rings offer unique electronic and hydrogen-bonding capabilities.
Purpose of the Study:
- To investigate the structural and dynamic effects of incorporating heteroaromatic spacer rings into tricyclic DNA bases.
- To understand how increased base polarizability and altered hydrogen bonding influence DNA helix conformation.
- To evaluate the impact of these modifications on base pairing, stacking, and intercalation.
Main Methods:
- Molecular dynamics (MD) simulations using modified AMBER force field parameters.
- Quantum mechanical AM1 calculations to determine base polarizability.
- Simulation of DNA oligomers (10-mers and 20-mers) with modified bases.
Main Results:
- Expanded bases with furan, pyrrole, or thiophene rings were successfully modeled.
- Increased base polarizability and altered hydrogen bonding were observed.
- MD simulations predicted a significantly larger major groove and negligible minor groove changes in 20-mers, resembling A-DNA.
- MD simulations of 10-mers indicated a shift towards base stacking and intercalation due to increased surface area and polarizability.
Conclusions:
- Heterospacer expansion of tricyclic bases significantly impacts DNA helix geometry, particularly the major groove.
- The modified bases exhibit altered electronic properties and hydrogen bonding potential.
- These structural changes favor base stacking and intercalation over canonical base pairing in shorter DNA sequences.
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