Simulations of a protein fold switch reveal crowding-induced population shifts driven by disordered regions.

ABSTRACT: Macromolecular crowding effects on globular proteins, which usually adopt a single stable fold, have been widely studied. However, little is known about crowding effects on fold-switching proteins, which reversibly switch between distinct folds. Here we study the mutationally driven switch between the folds of G_A and G_B, the two 56-amino acid binding domains of protein G, using a structure-based dual-basin model. We show that, in the absence of crowders, the fold populations P_A and P_B can be controlled by the strengths of contacts in the two folds, κ_A and κ_B. A population balance, P_A ≈ P_B, is obtained for κ_B/κ_A = 0.92. The resulting model protein is subject to crowding at different

SUBMITTER: Bazmi S 

PROVIDER: S-EPMC10492864 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature