title: Exploring the molecular basis of dsRNA recognition by Mss116p using molecular dynamics simulations and free-energy calculations.
abstract: DEAD-box proteins are the largest family of helicase that are important in nearly all aspects of RNA metabolism. However, it is unclear how these proteins recognize and bind RNA. Here, we present a detailed analysis of the related DEAD-box protein Mss116p-RNA interaction, using molecular dynamics simulations with MM-GBSA calculations. The energetic analysis indicates that the two strands of double strands RNA (dsRNA) are recognized asymmetrically by Mss116p. The strand 1 of dsRNA provides the main binding affinity. Meanwhile, the nonpolar interaction provides the main driving force for the binding process. Although the contribution of polar interaction is small, it is vital in stabilizing the protein-RNA interaction. Compared with the wild type Mss116p, two studied mutants Q412A and D441A have obviously reduced binding free energies with dsRNA because of the decreasing of polar interaction. Three important residues Lys409, Arg415 and Arg438 lose their binding affinity significantly in mutants. In conclusion, these results complement previous experiments to advance comprehensive understanding of Mss116p-dsRNA interaction. The results also would provide support for the application of similar approaches to the understanding of other DEAD-box protein-RNA complexes.
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xue
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhang
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.forename: Ying-Lu
authors.initials: YL
authors.lastname: Cui
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Chu
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D053487:DEAD-box RNA Helicases / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012330:RNA, Double-Stranded / Q000737:chemistry*; D012331:RNA, Fungal / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D012330:RNA, Double-Stranded; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; C058150:MSS116 protein, S cerevisiae; D053487:DEAD-box RNA Helicases