Abstract
Impact of the internucleotide linkage modification by inserting a methylene group to the P-O bond (-O-PO −2 -O- chain changed for -O-PO −2 -CH2-O-), on the modified oligonucleotide binding ability to the natural DNA strand was studied by molecular dynamics simulation. Complex of (dT)11 with a deoxyadenosine undecamer containing alternating modified and natural internucleotide linkage was studied as a model system. The Amber force field was completed by a set of new parameters needed to model the modified part of the nucleotide. The simulations confirmed existence of a double-helical complex the melting point of which is considerably higher than 300 K. While the thymidine (unmodified) strand possesses a B-type secondary structure, the conformation of the adenosine (modified) strand is not stable at 300 K. The -ggt conformation of the modified linkages is highly preferred, temporary jumps to the -g-gt and ggt conformations were, however, observed.
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This work was supported by the Grant Agency of Charles University (projects No. 105/95 and No. 24/B/97).
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Barvík, I., Štěpánek, J. & Bok, J. Molecular dynamics simulations of the oligonucleotide with the modified phosphate/phosphonate internucleotide linkage. Czech J Phys 48, 409–415 (1998). https://doi.org/10.1007/BF02690708
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DOI: https://doi.org/10.1007/BF02690708