text: In analogy to the rule of five, it has been proposed that ideal fragments should follow the rule of three (molecular weight < 300, ClogP < 3, the number of hydrogen bond donors and acceptors each should be < 3 and the number of rotatable bonds should be < 3).  Since the fragments have relatively low affinity for their targets, they must have high water solubility so that they can be screened at higher concentrations.