Structural aspects of formetanate hydrochloride binding with human serum albumin using spectroscopic and molecular modeling techniques

Formetanate Hydrochloride (FMT), a highly potent chemical, acts as an insecticide, acaricide, and miticide to protect various fruits and vegetables. The widespread use elevates concern about its presence in the ecosystem, impact upon human health via interaction with biological receptors. Spectroscopic and molecular modeling techniques at different temperatures were used to investigate the binding of FMT with Human serum albumin (HSA) at the molecular level. The experimental and computational results have provided the binding affinity, binding mode, conformational flexibility, and thermodynamic profile of FMT-HSA complex. The FMT binding appears to be spontaneous, and entropy driven. Overall binding affinity of FMT falls within-7.29 to-4.67 Kcal M-1. FMT binds in domain I, subdomain IA of HSA and is stabilized by hydrophobic interactions. Molecular dynamics simulations of the FMT-HSA complex over 100 ns at 288 K, 298 K and 308 K indicated that FMT showed minor adjustments in conformation and placement within the binding site. While, MM/PBSA analysis of the complex provided individual contributions of energy terms. Quantum mechanical (QM) calculations were used to calculate absolute energy values of different poses of FMT which in turn showed minor variations in energy suggesting slight conformational variation in the bound form. The computational results are in agreement with experimental findings.

Automated summary

The study on the binding affinity, binding mode, and conformational changes of Formetanate Hydrochloride (FMT) with Human serum albumin (HSA) indicates that FMT exhibits entropy-driven binding and moderate overall binding affinity.