Understanding the molecular interaction of human argonaute‐2 and miR‐20a complex: A molecular dynamics approach

Abstract Argonaute‐2 (AGO2), a member of the Argonaute family, is the only member possessing catalytic and RNA silencing activity. In here, a molecular dynamics (MDs) simulation was performed using the crystal structure of human AGO2 protein complex with miR‐20a. miR‐20a is involved with various kind of biological process like heart and lung development, oncogenic process, etc. In precise, MD simulation was carried out with AGO2 protein complex with wild type, two mutant sites and four mutant sites in guided microRNA (miRNA). It has been noted that root‐mean‐square deviation (RMSD) of atomic positions of nucleic acid for wild type and two mutant sites guided miRNA has the same pattern of fluctuations, which stabilizes around 0.27 nm after 2 ns. Cα atom of AGO2 protein in the complex shows that this complex with wild type and two mutant site mutation duplex has a stable RMSD value after 20 ns, ranging between 0.14 and 0.21 nm. From the root‐mean‐square fluctuation (RMSF), we observed an increased pattern of fluctuations for the atoms of four mutant complex of AGO2‐miR‐20a complex. This increased RMSF of non‐mutated nucleic acids is contributed by U‐A bond breaking at the site of the nucleotide of U2 of guided miRNA, as observed from the duplex structure taken at different time steps of the simulation. Superimposed structure of the miRNA‐mRNA duplex for the three complexes depicts that the three miRNA‐mRNA duplexes are stable during the simulation. Current work demonstrates the possible correlations between the conformational changes of this AGO2‐miR‐20a duplex structure and the interactions of different atoms.