Particle insertion. Hydrophobic effects are considered to play an important role in solvation phenomena such as protein stability and other self-assembly phenomena. Therefore, it is important to validate the capacity of each water model to reproduce hydrophobic behavior. Here, we probe the solvation free energies of methane for each water molecule by particle insertion methods. 109 The free energy of hydrophobic solvation for the insertion of the methane bead into each water model is presented in Figure . In general, most water models were within 2 kJ/mol of the experimental value, although there was a systematic overestimation of the value. The Class II models were an exception, but this may be due to the fact that it was necessary to extrapolate 12-6 Lennard-Jones parameters for these models in order to perform particle insertion. Interestingly, all of the 5-point models as well as some models with poorer overall agreement with the structural and dynamic properties studied here such as TIP3P and CVFF reproduced the free energy of hydrophobic solvation reasonably well. TIP3P has been found previously to predict hydration free energies of a range of small neutral organic molecules with an rms error of 1.24 kcal/mol. This further illustrates the difficulties in parameterizing a water model for all possible properties.