Figure 2.

Calculation of ΔG^{ternary(sterics)} by alchemical perturbation of BTK in the ternary complex of BTK-PROTAC (10)-CRBN. (a) TI and MBAR both reach apparent convergence in the time-forward and time-reversed directions with no pathological signs. The gray band in each panel represents the final estimation using 100% data ± 0.1 kT as a threshold for error tolerance, where k is the Boltzmann constant. (b) TI estimation is shown as the blue area under the curve of ⟨∂U/∂λ⟩. (c) TI, BAR, and MBAR agree for all intermediate ΔGs between adjacent states. All error bars of computational results here and in subsequent figures represent ±1 std. Color coding for TI, BAR, and MBAR results are the same in subsequent figures unless otherwise stated.