Figure 5.1.1 Energy spectrum for protein design

In order to design stable, unique, and soluble proteins, ∆G_gap = G_target - <G_alt/agg/unf> must be minimized. Consider two sequences X and Y. Sequence X was designed considering only the target (thick line) and unfolded (gradient; unf) states (a). However, there are other structures such as aggregates and alternative conformers (close-spaced lines; agg/alt) with even lower energies (b). In contrast, Sequence Y was designed considering these structures, and is less stable with respect to the unfolded state than Sequence X, but more stable compared to aggregates and alternative conformers (c). Adapted from Pokala and Handel 2005.