Computer simulation of secondary structure of biological and synthetic macromolecules

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Zhang, Wei
Ludovice, Peter J.
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RNA tetraloop is the smallest, simplest and the most frequent motif which is involved in numerous important biological functions. A local deviation from the RNA standard tetraloop, d2 tetraloop, has been identified with high abundance in 5S, 16S and 23S rRNAs. The presence of d2 tetraloops in highly conserved regions of 16S and 23S rRNAs suggests their functional importance. With one less residue in the loop, d2 tetraloops are considered more energetically restrained and less stable than standard tetraloops. The deletion at position j+2 in the loop is always correlated with adjacent stem distortion. MD simulations of 314-d2-tetraloop (a sample structure of d2 tetraloops) and cutd2-tetraloop (an artificially built perfect d2 tetraloop with no stem defects) have shown that stem defects are the stabilizing factor of d2 tetraloops. Simulations have also revealed that the insertion residue 318C (an example of stem defect) is stabilizing 314-d2-tetraloop by forming hydrogen bonding interactions with both the loop and the stem. When these two hydrogen bonding interactions are eliminated, the structure remained relatively stable compared to cutd2-tetraloop where the insertion residue was completely removed from the stem. This suggests the insertion residue is also stabilizing 314-d2-tetraloop by providing some conformational relaxation in the stem. Investigation of RNA standard tetraloop high temperature unfolding has revealed that the d2 tetraloop is possibly a kinetically trapped intermediate state during the folding of the standard tetraloop. High temperature unfolding simulations of standard tetraloop have shown a three-state folding behavior: a folded state, an intermediate state and an unfolded state. The folding of standard tetraloop starts with the formation of the loop. The closing base pair forms first, followed by the loop and the stem which form critical interactions such as base pairing and stacking that make a tetraloop. ROMP PNB has been investigated as supports to immobilize homogeneous catalysts to achieve both high reactivity and selectivity and easy separation. Polymers with intermediate conformational order can increase the accessibility of tethered homogeneous catalysts. Simulations of ROMP PNBDC_UD have shown the importance of bulky side groups in enabling the polymer to adopt a helical conformation. Such helical conformations have been associated with intermediate structural order in similar polymers such as PNB made by non-ROMP mechanisms. This intermediate order manifests itself as a split in the amorphous halo of WAXD pattern. Bulk simulations generated WAXD patterns that are close to the experimentally generated WAXD patterns where there are two split peaks: lower angle peak representing intermolecular interaction and higher angle peak representing intramolecular interaction.
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