| The grant project is devoted to the study on the impact of chemical modifications on structural and hybridization properties of synthetic analogues of nucleic acids. Main attention will be paid to finding of an optimal modification leading to the stabilization of double and triple helical structures by means of inter-strand interaction. This post-doc project is attached to the main project within the framework of which the enzymatic stable posphonate nucleotide analogues will be prepared. Nucleic acids with improved hybridization and enzymatic stability properties are interesting from the point of view of potential chemotherapeutic utilization by means of "antisense" mechanism (modified nucleic acid strand bind to a specific sequence of nucleotides in its mRNA target to inhibit production of the specific protein). The theoretical approach will be based on molecular dynamics (MD) technique, which allows simulations at non-zero temperature (typically 300 K), with atomic representation of solvent and ions. Nanosecond scale explicit solvent MD simulations will be used for investigation of double and triple helical structures of antisense oligonucleotides with RNA or DNA segments. |
