Imidazole-[1,5‑<i>a</i>]‑Pyridines Can Occupy the EGFR Allostery with a Strong Polar Interaction.

ABSTRACT: The imidazole-[1,5-a]-pyridine derivatives were recently synthesized and showed remarkable bioactivity against three cancer cell lines, but an understanding of their activities is still missing. To prompt a detailed investigation into their molecular binding mechanisms, we carried out a comprehensive computational workflow for structure-based drug design. The protocol encompasses (i) ligand polarization using quantum chemical calculations, (ii) docking algorithms to generate initial protein-ligand conformations, (iii) molecular dynamics simulations to evaluate ligand diffusion within the protein pocket, and (iv) binding free energy calculations through the umbrella sampling molecular dynamics method. The inherent flexibility of the epidermal growth factor receptor (EGFR) kinase prot

SUBMITTER: Truong DT 

PROVIDER: S-EPMC12917672 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature