Quantum Mechanical Studies of DNA and LNA

Quantum mechanical (QM) methodology has been employed to study the structure activity relations of DNA and locked nucleic acid (LNA). The QM calculations provide the basis for construction of molecular structure and electrostatic surface potentials from molecular orbitals. The topologies of the elec...

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Veröffentlicht in:Nucleic acid therapeutics 2014-04, Vol.24 (2), p.139-148
Hauptverfasser: Koch, Troels, Shim, Irene, Lindow, Morten, Ørum, Henrik, Bohr, Henrik G.
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container_end_page 148
container_issue 2
container_start_page 139
container_title Nucleic acid therapeutics
container_volume 24
creator Koch, Troels
Shim, Irene
Lindow, Morten
Ørum, Henrik
Bohr, Henrik G.
description Quantum mechanical (QM) methodology has been employed to study the structure activity relations of DNA and locked nucleic acid (LNA). The QM calculations provide the basis for construction of molecular structure and electrostatic surface potentials from molecular orbitals. The topologies of the electrostatic potentials were compared among model oligonucleotides, and it was observed that small structural modifications induce global changes in the molecular structure and surface potentials. Since ligand structure and electrostatic potential complementarity with a receptor is a determinant for the bonding pattern between molecules, minor chemical modifications may have profound changes in the interaction profiles of oligonucleotides, possibly leading to changes in pharmacological properties. The QM modeling data can be used to understand earlier observations of antisense oligonucleotide properties, that is, the observation that small structural changes in oligonucleotide composition may lead to dramatic shifts in phenotypes. These observations should be taken into account in future oligonucleotide drug discovery, and by focusing more on non RNA target interactions it should be possible to utilize the exhibited property diversity of oligonucleotides to produce improved antisense drugs.
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identifier ISSN: 2159-3337
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subjects Deoxyribonucleic acid
DNA
DNA - chemistry
Humans
Ligands
Models, Molecular
Molecular Structure
Nucleic Acid Conformation
Nucleic acids
Oligonucleotides - chemistry
Oligonucleotides, Antisense - chemistry
Original
Original Articles
Pharmacology
Quantum physics
Quantum Theory
Static Electricity
Thermodynamics
title Quantum Mechanical Studies of DNA and LNA
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