Predicting stable binding modes from simulated dimers of the D76N mutant of β 2-microglobulin.

ABSTRACT: The D76N mutant of the β 2 m protein is a biologically motivated model system to study protein aggregation. There is strong experimental evidence, supported by molecular simulations, that D76N populates a highly dynamic conformation (which we originally named I 2 ) that exposes aggregation-prone patches as a result of the detachment of the two terminal regions. Here, we use Molecular Dynamics simulations to study the stability of an ensemble of dimers of I 2 generated via protein-protein docking. MM-PBSA calculations indicate that within the ensemble of investigated dimers the major contribution to interface stabilization at physiological pH comes from hydrophobic interactions between apolar residues. Our structural analysis also reveals that the interfacial region associated

SUBMITTER: Oliveira NFB 

PROVIDER: S-EPMC8473664 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature