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Updated: Dec 15, 2025

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Mapping the underlying mechanisms of fibrinogen benzothiazole drug interactions using computational and experimental
Michael González-Durruthy1, Gustavo Scanavachi2, Ramón Rial3
1Soft Matter and Molecular Biophysics Group, Department of Applied Physics, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.
Abstract:
Three-dimensional conformational crystallographic binding-modes are of paramount importance to understand the docking mechanism of protein-ligand interactions and to identify potential "leading drugs" conformers towards rational drugs-design. Herein, we present an integrated computational-experimental study tackling the problem of multiple binding modes among the ligand 3-(2-Benzothiazolylthio)-propane sulfonic acid (BTS) and the fibrinogen receptor (E-region). Based on molecular docking simulations, we found that the free energy of binding values for nine of different BTS-docking complexes (i.e., BTS-pose_1-9) were very close. We have also identified a docking-mechanism of BTS-interaction mainly based on non-covalent hydrophobic interactions with H-bond contacts stabilizing the fibrinogen-BTS docking complexes. Interestingly, the different BTS-poses_1-9 were found to be able to block the fibrinogen binding site (E-region) by inducing local perturbations in effector and allosteric residues, reducing the degree of collectivity in its flexibility normal modes. As such, we theoretically suggest that the BTS-binding modes can significantly affect the physiological condition of the unoccupied fibrinogen protein structure by bringing global and local perturbations in the frequency domain spectra. The proposed theoretical mechanisms, the interactions involved and the conformational changes suggested, were further corroborated by different experimental techniques such as isothermal titration calorimetry (ITC), zeta potential, UV-vis, fluorescence and small angle X-ray scattering (SAXS). The combined results shall open new avenues towards the application of complex supra-molecular information in rational drugs-design.
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