Folding-upon-binding pathways of an intrinsically disordered protein from a deep Markov state model.

ABSTRACT: A central challenge in the study of intrinsically disordered proteins is the characterization of the mechanisms by which they bind their physiological interaction partners. Here, we utilize a deep learning based Markov state modeling approach to characterize the folding-upon-binding pathways observed in a long-time scale molecular dynamics simulation of a disordered region of the measles virus nucleoprotein N_TAIL reversibly binding the X domain of the measles virus phosphoprotein complex. We find that folding-upon-binding predominantly occurs via two distinct encounter complexes that are differentiated by the binding orientation, helical content, and conformational heterogeneity of N_TAIL. We do not, however, find evidence for the existence of canonical conformational

SUBMITTER: Sisk T 

PROVIDER: S-EPMC10401938 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature