The Allain lab (ETH Zurich) together with the Sponer group (Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic) has published a paper describing the role of water molecules in the RNA recognition by the RNA recognition motif (RRM) of the Fox-1 protein, which is a regulator of alternative splicing. Its RRM binds to a hexanucleotide RNA target sequence with high affinity and the structure of this complex was determined previously by the Allain lab using Nuclear Magnetic Resonance Spectroscopy (NMR) (Auweter S.D. et. al., (2006) EMBO Journal). This structure together with a high-resolution X-ray structure of the unbound RRM revealing bound water molecules provided the starting point for molecular dynamics (MD) simulations to further structurally study the role of water in RNA RRM recognition. Based on the results of the MD analyses two selected water binding sites were subsequently studied by NMR, affinity measurements and free-energy calculations. For one of the sites, which is evolutionarily conserved in RRMs, a quantitative agreement between the computational and experimental approaches was found demonstrating the value of MD analyses to analyze hydration patterns involved in RNA-protein recognition.