DFT calculations often neglect entropic contributions which typically favor dispersion of the dopants, and thus dopant-host combinations with aggregation and/or segregation energies that are negative but close to zero may still be accessible in experimental synthesis operated at elevated temperatures. Assuming a 0.25 eV entropic contribution, we identified 16 stable SAAs out of the 27 candidates studied, including 3d dopants of Sc/Cu, Cr/Cu, Mn/Cu, Ni/Cu, and Zn/Cu; 4d dopants of Y/Cu, Zr/Cu, Rh/Cu, Pd/Cu, Ag/Cu, and Cd/Cu; 5d dopants of Hf/Cu, Ir/Cu, Pt/Cu, Au/Cu, and Hg/Cu (Figure , SI Figure , and Table ). Unsurprisingly, several DFT-predicted stable SAAs have been successfully synthesized in recent experiments, demonstrating the robustness of our computational strategy to predict stability. For example, Ni/Cu SAA was prepared by a modified electroless galvanic deposition method and was characterized using X-ray powder diffraction (XRD), high-resolution transmission electron microscope (HRTEM), and scanning electron microscope (SEM) images for ethanol dehydrogenation. In another work, Rh/Cu SAA was synthesized and examined using multiple experimental techniques to understand the active single site, including low-temperature scanning tunneling microscopy (LS-STM), temperature programed desorption (TPD), and reflection absorption infrared spectroscopy (RAIRS). Using similar synthesis and characterization techniques, Pd/Cu SAA and Pt/Cu SAA have also been successfully prepared. In addition to experimental verification, our DFTpredicted stability of SAAs is consistent with other simulation studies. ). Here, we only focused on the adsorption sites around dopants since experimental work characterized them as the active sites. Starting from the most preferred adsorption sites, we first calculated reaction energies of CH4 dehydrogenation to *C on 16 stable SAAs (Figure , SI Table ). We observed that dopants can effectively tune the activity of C-H activation on Cu(111) host, resulting in a wide range of dehydrogenation energies: -0.51 eV (Hf/Cu) to 1.30 eV (Hg/Cu) for CH4 dehydrogenation; 0.18 eV (Ir/Cu) to 1.12 eV (Au/Cu) for *CH3 dehydrogenation; -0.22 eV (Ir/Cu) to 0.70 eV (Au/Cu) for *CH2 dehydrogenation; 0.33 eV (Ir/Cu) to 1.70 eV (Zn/Cu) for *CH dehydrogenation (SI Table ). The last dehydrogenation step, i.e., *CH to *C, is usually the least favorable step with highest reaction energies. In addition, we noted correlation between the C-H activation energies for the first two dehydrogenation steps (i.e., CH4 to *CH3 and *CH3 to *CH2) and the dopant's outer-shell d-electron configuration that reaction energies become more positive with increasing number of outer-shell d-electrons, while the other two dehydrogenation steps (i.e., *CH2 to *CH and *CH to *C) exhibit different trends that reaction energies become more negative first and then more positive with increasing number of d-electrons of dopants (SI Figure ). In general, SAAs with dopants from early and mid-row transition metals show surmountable reaction energies for CH4 dehydrogenation, while SAAs containing late transition metals from groups 11 and 12 consistently exhibit higher CH4 dehydrogenation energies. This trend suggests that SAAs containing dopants with almost filled d orbitals are not reactive for C-H bond activation.