Multi-state design of flexible proteins predicts sequences optimal for conformational change
Fig 1
Graphical representation of hypothesis and experimental design.
(A) Schematic of sequence space and the impact of flexibility on sequence tolerance. S1 and S2 represent two unique conformations of the same residue length separated by some RMSD that populate two local energy minima. Black lines with end caps represent unique sequences that are energetically most favorable for a single conformation. The dark shaded area encircles sequences that are energetically favorable for both conformations. Here we illustrate that by using multiple conformations during protein design, we identify sequences that are energetically suitable for conformational flexibility, yet are not necessarily the most stable sequence for any given conformation. Additionally, the requirement to adopt multiple conformations constrains the number of suitable sequences (B) Flow chart of benchmark design.