Grand Canonical Monte Carlo simulations were performed for single component isotherms of CO2 and CH4 in the p-tert-butylcalix[4]arene structure. Comparison with literature data for adsorption used the Peng-Robinson equation of state to map simulated fugacitics to experimentally determined pressures. CO2 binding in the high-pressure structure of TBC4 (TBC4-H) occurs in two distinct waves. The cage sites in TBC4 completely fill up, followed by the filling of interstitial sites, resulting in the sum of two Langmuir isotherms being the best way to describe the total absorption isotherms. Our simulation results capture the essential experimental feature that the cage sites are the major contributor to the absorption isotherms, and the contribution of interstitial sites are significantly less. We found that CH4 does not exhibit the same two-site binding characteristic and has a smaller temperature dependence, which arises from a smaller negative entropy change upon absorption compared with the case for CO2. Our calculations give higher binding than observed experimentally for the cage site but lower binding for the interstitial site. We also demonstrate that by resealing the interaction between CO2 and the lattice, the results can reproduce the experimental data well at low loadings, The resealed potentials are within the range found in other studies. This makes the discrepancy between experiment and simulation at high loadings greater, which is unexpected for this system. It is postulated that the simulation points to structural changes or defects being partially responsible for the relatively higher absorption found experimentally.