The conformation of the methylene blue (MB)-guanine (GUA) complex in water was investigated by molecular dynamics simulation. It was found that the T-shaped vacuo stable conformation becomes unstable in water and turns into a well-defined stacked conformation. The free energy of the complex formation was determined by the thermodynamic integration method and found equal to -7.2 +/- 0.2 kcal/mol. The variation of the hydration energy upon complexation was found to be positive (about 14 kcal/mol), being compensated by the solute-solute interaction energy (about -21 kcal/mol). The main contribution to this solute-solute interaction energy arises from the van der WaaIs forces (about -14 kcal/mol).