Identification of novel chemical scaffolds against kinase domain of cancer causing human epidermal growth factor receptor 2: a systemic chemoinformatic approach

Abstract

The Human epidermal growth factor receptor 2 (HER2) is expressed in high magnitude in several cancers. Designing new drug molecules that target kinase domain of the HER2 enzyme might provide an appealing platform. Considering this, herein, a multi-phase bioinformatic approach is applied to screen diverse natural and chemical scaffolds to identify compounds that fit best at the kinase domain of HER2. By doing so, three compounds; LAS_51187157, LAC_51217113, LAC_51390233 were pointed with docking score of −11.4 kcal/mol, −11.3 kcal/mol and −11.2 kcal/mol, respectively. In molecular dynamic simulation, the complexes behaved in a stable dynamic with no major local/global structural variations. The intermolecular binding free energies were further estimated that concluded LAC_51390233 complex was the most stable and has less entropy energy. The good docked affinity of LAC_51390233 with HER2 was confirmed by WaterSwap absolute binding free energy. The entropy energy demonstrated that LAC_51390233 has less freedom energy compared to others. Similarly, all three compounds revealed very favorable druglike properties and pharmacokinetics. All the selected three compounds were also non-carcinogenic, non-immunotoxicity, non-mutagenicity, and non-cytotoxic. In a nutshell, the compounds are interesting scaffolds and might be subjected to extensive experimental testing to reveal their real biological potency.

Communicated by Ramaswamy H. Sarma

Keywords:

• Human epidermal growth factor receptor 2
• kinase domain
• virtual screening
• Lac_51390233
• molecular dynamics simulation
• WaterSwap

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.