A theoretical approach on ADMET properties of an azo-ester based fluorophore (AEF), and it's energetics, binding stability and molecular interactions with select globular proteins

Molecular docking (Mol.Doc) approach of an azo-ester based fluorophore (AEF) with widely studied proteins like Human serum Albumin (HSA), Bovine serum Albumin (BSA), Beta lactoglobin (βLG) and Ovalbumin (OVA) were carried out. The binding affinity and strength of AEF-HSA complex is due to hydrogen-bonding (h-bonding) and hydrophobic interactions (predominantly attributed to pi-alkyl). AEF and HSA acts as h-bonding acceptor as well as donor. The energetically favored conformers of AEF-HSA complex are governed and stabilized by polar as well as non-polar amino acids. On the contrary, the pattern observed in all the conformers of AEF-BSA, AEF- βLG and AEF-OVA are energetically least favored (+ve ∆G) compared to that of HSA. The least binding affinity of AEF is towards OVA (Binding energy (BE) +581.15 Kcalmol⁻¹ followed by βLG (+55.11) and BSA (+12.12) . Though BSA and HSA are structurally similar to each other, they vary in the binding stability with AEF. This is attributed to several unfavorable interactions that destabilize AEF-BSA complex which was not resulted in the complex existing between AEF-HSA. The energetically least stable complexes (AEF-BSA, AEF-βLG and AEF-OVA) are predominantly governed by hydrophobic interactions. However, several h-bonding interactions along with pi-sigma/pi-pi/pi-alkyl interactions result in destabilization of the above complexes. Interestingly, AEF-HSA complex stability is attributed to fewer number of hydrophobic interactions along with h-bonding interactions. The h-bonding interaction governs the stability of the complex which is the driving force. Docking studies illustrates that the binding of amino acids (AAs) in various subdomains play a significant role on the binding nature. The stability of AEF-HSA over other protein complexes in terms of BE is emphasized in the study. The energetically stable sites and sub-domains of AEF with HSA and BSA establish the site selective and site-specific nature of AEF with proteins. In silico studies provide an excellent and easier approach in establishing the molecular interactions existing between AEF with globular proteins. ADMET parameters of the guest molecule calculated exemplifies that AEF compound is less toxic and possesses high oral bioavailability. Based on the binding efficiency of AEF with albumins, the ADMET properties and drug likeliness approach of AEF provides an information on the application towards proteins in the concept of medicine and chemistry.