It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugs
Fig 2
Non-native entanglement was formed due to loss of the native entanglement.
The 80% most probable CAT-III post-translational pathways for (a) native folding and (b) misfolding are shown as a transition network with arrows indicating transitions from one state to another. Each node represents a state, and a representative structure of each state is presented, with the state ID at the top right corner. Structures without gain of non-native entanglements are shown in cyan, while the non-native entanglements are shown in red on the closed loop and blue on the threading segment, with the rest of the protein in white. Four values are presented near each node, representing 〈Q1|3〉 (orange), 〈Q2|5〉 (green), 〈Ggain〉 (red) and 〈Gloss〉 (blue). (c) Native structure of CAT-III (PDB ID: 3CLA) with five segments represented in different colors. (d) A portion of the co-translational folding pathways of DDLB starting from state C7, which is separated into a misfolding pathway (top) and a native folding pathway (bottom). All the representations are the same as in panels (a) and (b), except for the inclusion of a white surface to depict the ribosome in each state, as non-native entanglements form co-translationally for this protein [3].