The Theoretical And Conputational Study Of ADAR2dsRBM/dsRNA Complex

RNA editing plays an important role in realizing the full potential of a given genome. Different from RNA splicing, RNA editing is just to fine-tune the sequence of RNA by changing only one or two nucleotides. A-I editing (deamination of adenosine (A) to create inosine (Ⅰ)) is best characterized in mammals and occurs in the regions of double-stranded RNA (dsRNA). Adenosine deaminases acting on RNA (ADARs) are members of a family of enzymes involved in A-I deamination editing in numerous mRNA and pre-mRNA transcripts. Recently, a solution structure of the ADAR2/GluR-2pre-mRNA complex is determined, and shed light on the mechanism under recognition process. This work uses MD simulation to study the dynamics of this structure and finds the following major points:1) The dynamics of editing R/G site is very important for conformation changes of pre-mRNA.2) Mismatch helps wild-type structure bind dsRNA more tightly. Without mismatch, protein slides along the sequence of dsRNA more easily and makes it more difficult for protein binding to dsRNA.3), There is strong correlative interaction between dsRBMs from ADAR2and GluR-2pre-mRNA.