Fig. 3: Ubiquitin-SH3c binding mechanism in the Markov state model.

a Reactive flux along the dominant binding pathways, minor flux states are omitted from visual representation for clarity. The magnitude of the flux along different binding pathways is represented qualitatively by the width of the arrows that interconnect the states. Ubiquitin is shown in red in Markov states in which it predominantly adopts the extended C-terminal conformation P₂. In the unbound state with compact C-terminal conformation P₁, ubiquitin is shown in blue. SH3c as ligand L is shown in cyan. The relative probabilities of the compact and extended C-terminal conformation in the different states are indicated in blue and red. The probabilities p_bind of the Markov states for reaching the native bound state prior to the fully unbound state are given at the bottom. b Coarse view of the binding mechanism with the unbound ubiquitin states P₁ and P₂ and the binding transition state P₂L^† and bound state P₂L in which ubiquitin predominantly adopts the conformation P₂ with extended C-terminus. The binding transition state P₂L^† includes all Markov states with intermediate binding probabilities 0.45 < p_bind < 0.75. c Representative ubiquitin structures with extended and compact C-terminus. Interactions that stabilize the compact C-terminal conformation are illustrated at the right.