Coevolution combined with molecular dynamics simulations provides structural and mechanistic insights into the interactions between the integrator complex subunits.

ABSTRACT: Finding the 3D structure of large, multi-subunit complexes is difficult, despite recent advances in cryo-EM technology, due to remaining challenges to expressing and purifying subunits. Computational approaches that predict protein-protein interactions, including Direct Coupling Analysis (DCA), represent an attractive alternative for dissecting interactions within protein complexes. However, they are readily applicable only to small proteins due to high computational complexity and a high number of false positives. To solve this problem, we proposed a modified DCA approach, a powerful tool to predict the most likely interfaces of protein complexes. Since our modified approach cannot provide structural and mechanistic details of interacting peptides, we combine it with Molecular Dynamics (M

SUBMITTER: Fongang B 

PROVIDER: S-EPMC10700540 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature