COMPUTATIONAL INVESTIGATION OF THE INTERACTIONS OF THE RISDIPLAM MOLECULE USED IN SMA TREATMENT WITH SHORT NUCLEIC ACID SEQUENCES
Project no. 23168 · Status: Kapanmış (Yayın bekleniyor) · 2021
Summary
<p>In this thesis, the interactions between Risdiplam molecule used in the treatment of SMA disease and 11 Ribodinucleotides formed by splitting the pre-mRNA Exon7 sequence corresponding to SMN2 gene into dinucleotides (GG, UU, AA, UA, AG, GA, AC, CA, UC, GU, AU), binding sites, energies and changes in their conformers were computationally analyzed. It was aimed to elucidate the interaction mechanism in line with the results obtained from the interaction of Risdiplam and Ribodinucleotides.</p><p>In the computational study, firstly, the conformational analysis of Risdiplam was performed. Combinations of the most stable conformer of Risdiplam and 11 ribodinucleotides (AA-R, GG-R, UU-R, AG-R, UA-R, AC-R, GA-R, CA-R, UC-R, GU-R, AU-R) were created and 14 possible structures from each combination were optimized in the water phase using the DFT /ωB97XD/6-31+G(d,p) basis set and the most stable structures were determined. The bonding sites, bond types and bond strengths between the molecules were calculated. In addition, binding energies were obtained by molecular docking studies. As a result, Risdiplam molecule showed the best binding affinity with CA Ribodinucleotide. Molecular docking results were in agreement with the DFT results. </p>