Fig. 5

Structural characterization of AGO2-siRNA interactions through molecular docking and MD simulations. (a) Molecular docking of selected siRNA candidates with the Argonaute protein (AGO2). Surface representations illustrate the binding conformations of siRNAs (magenta) within the Argonaute complex, with its PAZ domain (light brown) and MID domain (light pink). Each siRNA adopts a unique orientation and interaction pattern, indicating potential variability in Argonaute loading efficiency and RISC complex formation. (b) Molecular dynamics (MD) simulation of top-ranked docked complexes for siRNA8 and siRNA12. The left panels show the docked AGO2-siRNA complexes, while the right panels depict the siRNA structures color-mapped according to root mean square fluctuation (RMSF) values (in nm), highlighting nucleotide-level flexibility. Increased RMSF values (red) indicate regions of higher structural mobility, potentially influencing target recognition or silencing efficiency. (c) Per-residue confidence scores (pLDDT) of the AlphaFold-predicted AGO2 structure (UniProt ID: Q9UKV8). The ribbon representation is color-coded according to pLDDT scores: very high confidence (≥ 90) in dark blue, high (70–89) in light blue, low (50–69) in yellow, and very low (< 50) in orange.