De novo Design of G Protein-Coupled Receptor 40 Peptide Agonists for Type 2 Diabetes Mellitus Based on Artificial Intelligence and Site-Directed Mutagenesis.

ABSTRACT: G protein-coupled receptor 40 (GPR40), one of the G protein-coupled receptors that are available to sense glucose metabolism, is an attractive target for the treatment of type 2 diabetes mellitus (T2DM). Despite many efforts having been made to discover small-molecule agonists, there is limited research focus on developing peptides acting as GPR40 agonists to treat T2DM. Here, we propose a novel strategy for peptide design to generate and determine potential peptide agonists against GPR40 efficiently. A molecular fingerprint similarity (MFS) model combined with a deep neural network (DNN) and convolutional neural network was applied to predict the activity of peptides constructed by unnatural amino acids (UAAs). Site-directed mutagenesis (SDM) further optimized the peptides to form specifi

SUBMITTER: Chen X 

PROVIDER: S-EPMC8236607 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature