Performance evaluation of functionalized linear peptides as potential vascular endothelial growth factor receptor inhibitors: an insilico approach

Abstract

Breast tumors have caused significant devastation in females worldwide, presenting a great challenge to researchers. In this regard, the primary goal of researchers is to design and develop efficient drug-like compounds that can act as anti-vascular endothelial growth factor receptor agents that can down-regulate cancer. It was investigated how functionalized linear peptides inhibited vascular endothelial growth factor receptors. To optimize the investigated peptides, density functional theory using the 6-31G* basis set was used. Molecular docking was done to perform molecular assessments of the peptides under study as well as the vascular endothelial growth factor receptor (PDB ID: 2vpf). ADMET screening was also done using AdMETLab to evaluate the pharmaceutical properties and the toxicity status of the peptides. The optimized investigated compounds yielded several descriptors, such as frontier molecular orbitals (highest occupied molecular orbital energy and lowest occupied molecular orbital energy), band gap, polar surface area, polarizability, lipophilicity, and many more which revealed the inhibiting potential of these compounds to act as anti-vascular endothelial growth factor receptor agent. Furthermore, the computed binding affinity showed that, in comparison to the reference medications (5-fluorouracil), the investigated compounds showed greater inhibition of the vascular endothelial growth factor receptor. Molecular dynamic simulation was used to validate the findings. The ADMET screening revealed that the studied compounds are safer and more bioavailable than the referenced drug