Computational design and characterization of nanobody-derived peptides that stabilize the active conformation of the β₂-adrenergic receptor (β₂-AR).

ABSTRACT: This study aimed to design and functionally characterize peptide mimetics of the nanobody (Nb) related to the β₂-adrenergic receptor (β₂-AR) (nanobody-derived peptide, NDP). We postulated that the computationally derived and optimized complementarity-determining region 3 (CDR3) of Nb is sufficient for its interaction with receptor. Sequence-related Nb-families preferring the agonist-bound active conformation of β₂-AR were analysed using the informational spectrum method (ISM) and β₂-AR:NDP complexes studied using protein-peptide docking and molecular dynamics (MD) simulations in conjunction with metadynamics calculations of free energy binding. The selected NDP of Nb71, designated P3, was 17 amino acids long and included CDR3. Metadynamics calcul

SUBMITTER: Sencanski M 

PROVIDER: S-EPMC6851183 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature