Paper Citing NAMD - Abstract
Xia, Zhen; Tien Huynh; Ren, Pengyu; Zhou, Ruhong
Large Domain Motions in Ago Protein Controlled by the Guide DNA-Strand Seed Region Determine the Ago-DNA-mRNA Complex Recognition Process
PLOS ONE, 8 Art. No. e54620, JAN 29 2013
The recognition mechanism and cleavage activity of argonaute (Ago), miRNA, and mRNA complexes are the core processes to the small non-coding RNA world. The 59 nucleation at the 'seed' region (position 2-8) of miRNA was believed to play a significant role in guiding the recognition of target mRNAs to the given miRNA family. In this paper, we have performed allatom molecular dynamics simulations of the related and recently revealed Ago-DNA: mRNA ternary complexes to study the dynamics of the guide-target recognition and the effect of mutations by introducing "damaging" C? C mismatches at different positions in the seed region of the DNA-RNA duplex. Our simulations show that the A-form-like helix duplex gradually distorts as the number of seed mismatches increases and the complex can survive no more than two such mismatches. Severe distortions of the guide-target heteroduplex are observed in the ruinous 4-sites mismatch mutant, which give rise to a bending motion of the PAZ domain along the L1/L2 "hinge-like" connection segment, resulting in the opening of the nucleic-acid-binding channel. These long-range interactions between the seed region and PAZ domain, moderated by the L1/L2 segments, reveal the central role of the seed region in the guide-target strands recognition: it not only determines the guide-target heteroduplex's nucleation and propagation, but also regulates the dynamic motions of Ago domains around the nucleic-acid-binding channel.
