Application of a genetic algorithm in the conformational analysis of methylene-acetal-linked thymine dimers in DNA: Comparison with distance geometry calculations |
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Authors: | Mischa L.M. Beckers Lutgarde M.C. Buydens Jeroen A. Pikkemaat Cornelis Altona |
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Affiliation: | (1) Laboratory for Analytical Chemistry, Catholic, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands;(2) Leiden Institute of Chemistry, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands |
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Abstract: | The three-dimensional spatial structure of a methylene-acetal-linked thymine dimer presentin a 10 base-pair (bp) sense–antisense DNA duplex was studied with a geneticalgorithm designed to interpret NOE distance restraints. Trial solutions were represented bytorsion angles. This means that bond angles for the dimer trial structures are kept fixed duringthe genetic algorithm optimization. Bond angle values were extracted from a 10 bpsense–antisense duplex model that was subjected to energy minimization by means ofa modified AMBER force field. A set of 63 proton–proton distance restraints definingthe methylene-acetal-linked thymine dimer was available. The genetic algorithm minimizesthe difference between distances in the trial structures and distance restraints. A largeconformational search space could be covered in the genetic algorithm optimization byallowing a wide range of torsion angles. The genetic algorithm optimization in all cases ledto one family of structures. This family of the methylene-acetal-linked thymine dimer in theduplex differs from the family that was suggested from distance geometry calculations. It isdemonstrated that the bond angle geometry around the methylene-acetal linkage plays animportant role in the optimization. |
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Keywords: | Genetic algorithm Distance geometry Methylene-acetal linkage |
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