COMP 268 |
| A PNA molecule is a DNA strand where the sugar-phosphate backbone has been replaced by a structurally homomorphous pseudopeptide chain consisting of N (2-amino-ethyl)-glycine units. PNA binds strongly to both DNA and RNA. However, an analysis of the X-ray and NMR data show that the dihedral angles of PNA/DNA or PNA/RNA complexes are very different from those of DNA/DNA or RNA/RNA complexes. In addition, the PNA strand is very flexible. One way to improve the binding affinity of PNA for DNA/RNA is to design a more preorganized PNA structure. An effective way to rigidify the PNA strand is to introduce ring structures into the backbone. In several experimental studies, the ethylenediamine portion of aminoethylglycine peptide nucleic acids (aegPNAs) has been replaced with one or more (S,S)-trans cyclopentyl (cpPNA) and (1S,2R)-cyclohexyl (chPNA) units. This substitution has met with varied success in terms of DNA/RNA recognition. In the present work we use molecular dynamics simulations to determine why some rings improve binding while others do not and to determine the contributions of both entropy and dihedral angle preference to the observed stronger binding. In addition, preliminary results on the effect of sequence on PNA dynamics and binding will also be presented. |
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Poster Session
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Ballroom Foyer, Poster
Sci-Mix
Division of Computers in Chemistry |