incorporating-target-protein-structure-flexibility-dynamics

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

The drug discovery process is a rigorous, time-consuming, and expensive operation. The computational approach in drug discovery allows researchers to ...

Universiti Malaya

The research examined the molecular interaction between nirmatrelvir (NIR), a drug used to treat COVID-19, and human serum albumin (HSA) using various techniques, , isothermal titration calorimetry (ITC), absorption, fluorescence, CD spectroscopy, and atomic force microscopy (AFM). ITC analysis showed that the NIR-HSA system possessed a moderate binding affinity, with a   value of 6.53 ± 0.23 × 10 M at a temperature of 300 K. The thermodynamic values demonstrated that the NIR-HSA complex was stabilized by hydrophobic contacts, hydrogen bonds, and van der Waals forces. The research also discovered modifications in the UV-Vis absorption spectrum of the protein as well as swelling of the HSA molecule when exposed to NIR, based on AFM results. The three-dimensional fluorescence spectral data indicated changes in the microenvironment around HSA's Trp and Tyr residues. Alterations in the protein structure (both secondary and tertiary structures) of HSA after NIR binding were verified using CD spectral studies in the far-UV and near-UV regions. The identification of the NIR binding site in subdomain IB (Site III) of HSA was predicted through competitive displacement experiments.

Assessing the molecular interaction between a COVID-19 drug, nirmatrelvir, and human serum albumin: calorimetric, spectroscopic, and microscopic investigations.

Ahmad Fadhlurrahman Ahmad Hidayat

Biography

JoVE Journal Publications

Other Publications