Directed self-assembly of block copolymers on chemical patterns is of considerable interest for sublithographic patterning. The concept of pattern interpolation, in which a subset of features patterned on a substrate is multiplied through the inherent morphology of an ordered block copolymer, has enabled fabrication of extremely small, defect-free features over large areas. One of the central challenges in design of pattern interpolation strategies is that of identifying system characteristics leading to ideal, defect-free directed assembly. In this work we demonstrate how a coarse-grained many-body model of block copolymers, coupled to an evolutionary computation (EC) strategy, can be used to design and optimize substrate-copolymer combinations for use in lithographic patterning. The proposed approach is shown to be significantly more effective than traditional algorithms based on random searches, and its results are validated in the context of recent experimental observations. The coupled simulation-evolution method introduced here provides a general and efficient method for potential design of complex device-oriented structures.