Computational fragment-based approaches have been widely used in drug design and drug discovery. One of the limitations for their application is the lack of performance of the scoring functions. With the emergence of new fragment-based approaches for single-stranded RNA ligands, we propose an analysis of the docking power of an MCSS-based approach evaluated on nucleotide binding sites. Combined with a clustering of MCSS-generated poses and some state-of-the-art scoring functions , the results suggest that it could be used in the design of oligonucleotides. MCSS | ligand binding | docking | scoring | protein-nucleotide interactions | FBD Correspondence: fabrice.leclerc@i2bc.paris-saclay.fr