Structural Bioinformatics Studies On The Chemical Modification Of DNA And RNA

DNA and RNA are important biomacromolecules in organisms.DNA carries genetic information. RNA manages multiple functions,which is transcribed from DNA. Chemical modifications occur on naturalDNA and RNA to regulate their performance. It will help a lot indeveloping new biological technology and therapy methods if theregulation mechanisms are clarified. Here we conducted structuralbioinformatics methods to study the effect of phosphorothioate on DNAhelix and the influence of isonucleotides on RNA interference.Sulfur modification of DNA is an endogenous chemical modification,which is discovered recently. However, the structure and function of themodification is not clear so far. In this paper, first we carried outconformation search of sulfur-modified dinucleotide and normaldinucleotide by molecular mechanics method. Then the conformers areoptimized by quantum mechanics method. After that, The backboneparameters of the optimized conformers are measured and were used to build up scoring functions. Finally, the backbone parameters of structuresfrom NDB were collected and evaluated by the scoring functions. Wefound that R-configure sulfur modification, the natural existence of sulfurmodification, will destabilized B-helix of DNA.Modified nucleotides are usually applied in RNA interference inorder to improve the stability and delivery of siRNA in vivo. In thisresearch, we checked the effect of isonucleotides on Ago/siRNA complexusing molecular dynamics simulation. We found that differentisonucleotides will affect the release of siRNA cleavage product bychanging the open-close movement of PAZ domain in Ago protein，andthen influence the RNA interference activity.