Computational evolution of an RNA-binding protein towards enhanced oxidized-RNA binding

Elucidation of the conformational dynamics and assembly of Argonaute–RNA complexes by distinct yet coordinated actions of the supplementary microRNA

“…Although the crystal structure of supplementary pairing in the AGO complex has been solved, it is challenging to provide enough information for elucidating the mechanism of supplementary pairing with only one averaged snapshot because of the limited conformational changes. Molecular dynamics (MD) simulations that explore protein and nucleic acid conformational dynamics at the atomic level are critical for understanding of target repression and TDMD process [37] , [38] , [39] , [40] , [41] , [42] , [43] . In the recent work, we have used MD simulations to directly uncover biomolecular mechanisms and protein–ligand/protein or protein–DNA/RNA recognitions [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] .…”

Characterization of epitranscriptome reader proteins experimentally and in silico: Current knowledge and future perspectives beyond the YTH domain

“…This synergistic experimental and computational approach, along with current techniques to generate the necessary protein and RNA structures, represents a starting point for further investigation of protein interactions with RNA modifications at an atomistic scale. Importantly, this platform served as a steppingstone for solving the “inverse problem” of examining the interaction of PNPase with 8-oxoG in atomic detail to provide insights into the mechanism of 8-oxoG discrimination [129] . Particularly, computations were employed to evolve PNPase for higher 8-oxoG affinity by screening mutants from a library of beneficial mutations and assessed their interactions using MD simulations [128] .…”

8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification

“…3c ). Increased PNPase binding to o 8 G, designed by computational evolution, renders cells resistant to H 2 O 2 treatment 152 . This evidence suggests that PNPase can directly recognize o 8 G-RNA and trigger its degradation to tolerate oxidative stress.…”