The study of EGFR-ligand complex electron property relationship with biological activity

Abstract

The present investigation grounded on estimation of electron properties of the structures of EGFR proteins-ligand complexes using our laboratory-developed methodology AlteQ approach, which describes the molecular electron density of the complex in space for a certain point in three-dimensional coordinates. Briefly, the system embodies molecular electron density as a sum of Slater’s type atomic increments of the molecular system. Further, using this methodology, we calculated different electron characteristics of selected EGFR protein-ligand complexes and established the relationship between different electron properties with their experimental pharmacological activity value (pIC₅₀). The study suggested that EGFR inhibitory activity has higher correlation with intermolecular contacts of H with pi-system of aromatic ring between protein and ligands. Therefore, this created model has impact to identify and design potential ligands against EGFR in anticancer drug discovery.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• EGFR-ligand complex
• quantum theory of atoms in molecules
• AlteQ approach
• electron properties

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The project was supported by Act 211, Government of the Russian Federation, contract 02.A 03.21.0011, and Ministry of Science and Higher Education of Russia (Grant no. FENU-2020-0019).