The therapeutic treatment of a patient using intensity-modulated proton therapy is described. In one example, a method of creating a proton treatment plan is presented that divides volumes of interest into sub-volumes, applies dose constraints to the sub-volumes, finds one or more feasible configurations of a proton therapy system, and selects a proton beam configuration that improves or optimizes one or more aspects of proton therapy. In some implementations, the method of dividing volumes into sub-volumes includes creating fractional sub-volumes based at least in part on proximity to a target volume boundary. In some implementations, the method of finding an improved or optimal proton beam configuration from a set of feasible configurations includes finding a minimum of a cost function that utilizes weighting factors associated with treatment sites.