Computer simulation of complexation of actinocin derivative and double stranded polyribocytidylic acid
Abstract
Relying on the results of molecular docking and on the known experimental data regarding complexation of actinocin derivative (ActIII) and double stranded polyribocytidylic acid (polyrC), five most probable ActIII - polyrC complexes are obtained. In these complexes target-ligand interactions are minimal and intermolecular hydrogen bonds are formed between donor-acceptor groups of ActIII and polyrC. Cytosine groups and/or oxygen atoms of sugarphosphate backbone of polyrC participate in hydrogen bonding with NH2, C=O, NH-groups of phenoxazone chromophore, and aminoalkyl side chains of ActIII. The influence of solvent-water molecules on the structure of complexes obtained using molecular docking is determined by the Monte Carlo method. The simulation is carried out taking into account 800 water molecules. It is shown, that water molecules can additionally stabilize polynucleotide target-ligand complexes by forming bridges between their donor-acceptor groups. Based on the analysis of simulation and experimental results, one of the ActIII - polyrC complexes is selected as the most probable one.
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