One possible reason for this is the neglect of temperature effects. This observation is also true for the hydrogen bonded base-pairs studied in this work. The experimentally determined force to unzip guanine-cytosine was reported to be 20 ± 3 pN, whereas the force to unbind adenine-thymine pairs is 9 ± 3 pN. This is again one order of magnitude smaller than predicted by the CoGEF methods, independent on the functional used.