In Silico Strategy for Targeting the mTOR Kinase at Rapamycin Binding Site by Small Molecules.

ABSTRACT: Computer aided drug-design methods proved to be powerful tools for the identification of new therapeutic agents. We employed a structure-based workflow to identify new inhibitors targeting mTOR kinase at rapamycin binding site. By combining molecular dynamics (MD) simulation and pharmacophore modelling, a simplified structure-based pharmacophore hypothesis was built starting from the FKBP12-rapamycin-FRB ternary complex retrieved from RCSB Protein Data Bank (PDB code 1FAP). Then, the obtained model was used as filter to screen the ZINC biogenic compounds library, containing molecules derived from natural sources or natural-inspired compounds. The resulting hits were clustered according to their similarity; moreover, compounds showing the highest pharmacophore fit-score were chosen from eac

SUBMITTER: Vittorio S 

PROVIDER: S-EPMC7922000 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature