Molecules, Vol. 25, Pages 5425: Targeting Beta-Blocker Drug –Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study

Molecules, Vol. 25, Pages 5425: Targeting Beta-Blocker Drug–Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study Molecules doi: 10.3390/molecules25225425 Authors: Michael González-Durruthy Riccardo Concu Laura F. Osmari Vendrame Ivana Zanella Juan M. Ruso M. Natália D.S. Cordeiro In this work, one of the most prevalent polypharmacology drug–drug interaction events that occurs between two widely used beta-blocker drugs—i.e., acebutolol and propranolol—with the most abundant blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as complementary tools. A fibrinogen crystallographic validation for the three best ranked binding-sites shows 100% of conformationally favored residues with total absence of restricted flexibility. From those three sites, results on both the binding-site druggability and ligand transport analysis-based free energy trajectories pointed out the most preferred biophysical environment site for drug–drug interactions. Furthermore, the total affinity for the stabilization of the drug–drug complexes was mostly influenced by steric energy contributions, based mainly on multiple hydrophobic contacts with critical residues (THR22: P and SER50: Q) in such best-ranked site. Additionally, the DFT calculations revealed that the beta-blocker drug&...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research