Quantum Mechanical Studies of DNA and LNA

Troels Koch, Irene Shim, Morten Lindow, Henrik Orum, Henrik G. Bohr

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.
Original languageEnglish
JournalNucleic Acid Therapeutics
Volume24
Issue number2
Pages (from-to)139-148
Number of pages10
ISSN1545-4576
DOIs
Publication statusPublished - 2014

Keywords

  • Original Articles
  • antisense drug interaction
  • drug discovery
  • electrostatic potential
  • ligand structure
  • pharmacological property
  • DNA
  • locked nucleic acid LNA
  • oligonucleotides
  • RNA
  • 03502, Genetics - General
  • 04500, Mathematical biology and statistical methods
  • 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines
  • 10515, Biophysics - Biocybernetics
  • 12512, Pathology - Therapy
  • 22002, Pharmacology - General
  • Biochemistry and Molecular Biophysics
  • Computational Biology
  • quantum mechanical modeling mathematical and computer techniques
  • Models and Simulations
  • Molecular Genetics
  • Pharmacology

Cite this

Koch, Troels ; Shim, Irene ; Lindow, Morten ; Orum, Henrik ; Bohr, Henrik G. / Quantum Mechanical Studies of DNA and LNA. In: Nucleic Acid Therapeutics. 2014 ; Vol. 24, No. 2. pp. 139-148.
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abstract = "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.",
keywords = "Original Articles, antisense drug interaction, drug discovery, electrostatic potential, ligand structure, pharmacological property, DNA, locked nucleic acid LNA, oligonucleotides, RNA, 03502, Genetics - General, 04500, Mathematical biology and statistical methods, 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines, 10515, Biophysics - Biocybernetics, 12512, Pathology - Therapy, 22002, Pharmacology - General, Biochemistry and Molecular Biophysics, Computational Biology, quantum mechanical modeling mathematical and computer techniques, Models and Simulations, Molecular Genetics, Pharmacology",
author = "Troels Koch and Irene Shim and Morten Lindow and Henrik Orum and Bohr, {Henrik G.}",
year = "2014",
doi = "10.1089/nat.2013.0465",
language = "English",
volume = "24",
pages = "139--148",
journal = "Oligonucleotides",
issn = "1545-4576",
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Koch, T, Shim, I, Lindow, M, Orum, H & Bohr, HG 2014, 'Quantum Mechanical Studies of DNA and LNA', Nucleic Acid Therapeutics, vol. 24, no. 2, pp. 139-148. https://doi.org/10.1089/nat.2013.0465

Quantum Mechanical Studies of DNA and LNA. / Koch, Troels; Shim, Irene; Lindow, Morten; Orum, Henrik; Bohr, Henrik G.

In: Nucleic Acid Therapeutics, Vol. 24, No. 2, 2014, p. 139-148.

Research output: Contribution to journalJournal articleResearchpeer-review

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AU - Koch, Troels

AU - Shim, Irene

AU - Lindow, Morten

AU - Orum, Henrik

AU - Bohr, Henrik G.

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N2 - 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.

AB - 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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KW - quantum mechanical modeling mathematical and computer techniques

KW - Models and Simulations

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KW - Pharmacology

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