Discovery of Novel Hsp90 C-Terminal Inhibitors Using 3D-Pharmacophores Derived from Molecular Dynamics Simulations.

ABSTRACT: Hsp90 C-terminal domain (CTD) inhibitors are promising novel agents for cancer treatment, as they do not induce the heat shock response associated with Hsp90 N-terminal inhibitors. One challenge associated with CTD inhibitors is the lack of a co-crystallized complex, requiring the use of predicted allosteric apo pocket, limiting structure-based (SB) design approaches. To address this, a unique approach that enables the derivation and analysis of interactions between ligands and proteins from molecular dynamics (MD) trajectories was used to derive pharmacophore models for virtual screening (VS) and identify suitable binding sites for SB design. Furthermore, ligand-based (LB) pharmacophores were developed using a set of CTD inhibitors to compare VS performance with the MD derived models. Vir

SUBMITTER: Tomasic T 

PROVIDER: S-EPMC7555175 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature