FIGURE 2.

(A) Details of the mutation path from L ₁ shown in Figure 1B) to its CC to compute $\mathrm{\Delta }\mathrm{\Delta }{G}_{L_1\to [D{L}_1]-R_{CC}}^{\mathit{bind}}$ : (I) electrostatic interactions of the non-CC atoms are scaled to zero (three steps; step 1 in the diagram is the native, fully interacting ligand), (II) LJ interactions of the non-CC hydrogen atoms are turned off (one step), (III) LJ interactions of the three non-CC heavy atoms are turned off on an atom-by-atom basis (three steps), (IV) the last non-CC heavy atom is changed to the “junction” atom type X (one step), (V) the CC reached from L ₁ $(R_{c{c}_1})$ is adjusted to the one reached from L ₂ (cf. Figure 1B), in five steps. (B) Overview of the workflow when computing free energy differences with transformato.