la402354r_si_001.pdf (1.11 MB)
Exploring the Molecular Basis of dsRNA Recognition by Mss116p Using Molecular Dynamics Simulations and Free-Energy Calculations
journal contribution
posted on 2013-09-03, 00:00 authored by Qiao Xue, Ji-Long Zhang, Qing-Chuan Zheng, Ying-Lu Cui, Lin Chen, Wen-Ting Chu, Hong-Xing ZhangDEAD-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.