AI Article Synopsis
- Molecular dynamics simulations were conducted to explore the structural differences between the wild type U1A protein and several Phe56 mutant variants that bind to SL2 RNA with varying strengths.
- The results showed that the free form of U1A is more flexible compared to its complex with RNA, and mutations in the Phe56 position lead to altered hydrogen-bonding and van der Waals interactions, which affect binding affinity.
- Specifically, the Phe56Ala mutation impacts interactions throughout the U1A-RNA complex, while Phe56Leu and Phe56Trp mutations induce localized changes, highlighting the importance of both direct interactions and dynamic behavior in maintaining complex stability.
Article Abstract
Molecular dynamics (MD) simulations were carried out to compare the free and bound structures of wild type U1A protein with several Phe56 mutant U1A proteins that bind the target stem loop 2 (SL2) RNA with a range of affinities. The simulations indicate the free U1A protein is more flexible than the U1A-RNA complex for both wild type and Phe56 mutant systems. A complete analysis of the hydrogen-bonding (HB) and non-bonded (VDW) interactions over the course of the MD simulations suggested that changes in the interactions in the free U1A protein caused by the Phe56Ala and Phe56Leu mutations may stabilize the helical character in loop 3, and contribute to the weak binding of these proteins to SL2 RNA. Compared with wild type, changes in HB and VDW interactions in Phe56 mutants of the free U1A protein are global, and include differences in β-sheet, loop 1 and loop 3 interactions. In the U1A-RNA complex, the Phe56Ala mutation leads to a series of differences in interactions that resonate through the complex, while the Phe56Leu and Phe56Trp mutations cause local differences around the site of mutation. The long-range networks of interactions identified in the simulations suggest that direct interactions and dynamic processes in both the free and bound forms contribute to complex stability.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732173 | PMC |
| http://dx.doi.org/10.1002/bip.21616 | DOI Listing |
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