title: Contributions of 3'-overhang to the dissociation of small interfering RNAs from the PAZ domain: molecular dynamics simulation study.
abstract: RNA interference (RNAi) is a 'knock-down' reaction to reduce expression of a specific gene through highly regulated, enzyme-mediated processes. Small interfering RNAs (siRNAs) are RNA molecules that play an effector role in RNAi and can bind the PAZ domains present in Dicer and RISC. We investigated the interaction between the PAZ domain and the siRNA-like duplexes through dissociation molecular dynamics (DMD) simulations. Specifically, we focused on the response of the PAZ domain to various 3'-overhang structures of the siRNA-like duplexes. We found that the siRNA-like duplex with the 3' UU-overhang made relatively more stable complex with the PAZ domain compared to those with 3' CC-, AA-, and GG-overhangs. The siRNA-like duplex with UU-overhang was easily dissociated from the PAZ domain once the structural stability of the complex is impaired. Interestingly, the 3' UU-overhang spent the least time at the periphery region of the binding pocket during the dissociation process, which can be mainly attributable to UU-overhang's smallest number of hydrogen bonds.
authors.affiliation: Department of Microbiology, University of Ulsan College of Medicine, 388-1 PoongNap-dong Songpa-goo, Seoul 138-736, South Korea.
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Soo Nam
authors.initials: SN
authors.lastname: Lee
authors.forename: Chul Hyun
authors.initials: CH
authors.lastname: Joo
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.forename: Han Saem
authors.initials: HS
authors.lastname: Lee
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Yoon
authors.forename: Yoo Kyum
authors.initials: YK
authors.lastname: Kim
authors.forename: Han
authors.initials: H
authors.lastname: Choe
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex