Sampling the structure of the noncanonical lin-4:lin-14 microRNA:mRNA complex by molecular dynamics simulations

siRNA and microRNA (miRNA) are two classes of noncoding RNAs that carry out post-transcriptional gene regulation by interacting with the target mRNA. The structural features of siRNA/miRNA-mRNA complex play a crucial role in gene silencing. Here we have used computer modeling and simulation approach to (i) elucidate the possible structures of the partially complementary lin-4:lin-14 miRNA-mRNA complex and (ii) compare the structural features with the fully complementary lin-4:lin-14 siRNA-mRNA complex. The fully complementary siRNA complex maintains a canonical helical shape while the presence of mismatch base pairs and bulge induce a kinked structure in the miRNA complex. Docking of the simulated duplex models on to the argonaute protein gives a direct indication that in the siRNA-mRNA structure, the scissile phosphate of the mRNA strand is more accessible to the catalytic site as compared to the miRNA-mRNA structures, providing an explanation for the less prevalence of the cleavage in the later case.