XO stands for the extended ONIOM method, which allows overlapping layers and can be applied to problems that require a high‐level calculation not only for the active site of a partial system, but also for the entire system. A metric called “force‐error test” was introduced to guide the design of the appropriate XO model by Wenping Guo, Anan Wu, Igor Ying Zhang, and Xin Xu on page 2142. As shown on the cover, force errors (dark blue) are mainly distributed along the alpha‐1,4 linkages if this cooperativity of hydrogen‐bonds is broken during the fragmentation. Adding a “Hat” patch can greatly reduce the force errors, which guarantees a good description of the fully optimized geometry, total energy, and vibrational spectra of the whole system.