Methods for creating build sequences which are determined using computational chemistry algorithms to simulate mechanosynthetic reactions, and which may use the mechanosynthesis process conditions or equipment limitations in these simulations, and which facilitate determining a set of mechanosynthetic reactions that will build an atomically-precise workpiece with a desired degree of reliability. Included are methods for error correction of pathological reactions or avoidance of pathological reactions. Libraries of reactions may be used to reduce simulation requirements.