RT Journal Article
T1 Targeting Beta-Blocker Drug–Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study
A1 González Durruthy, Michael
A1 Concu, Riccardo
A1 Osmari Vendrame, Laura F.
A1 Zanella, Ivana
A1 Ruso Beiras, Juan Manuel
A1 Cordeiro, M. Natália D. S.
K1 Drug–drug interactions
K1 Beta-blocker drugs
K1 Polypharmacology
K1 Molecular docking
K1 DFT
K1 Ultrasound measurements
AB 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–drug complexes have a spontaneous thermodynamic stabilization following the same affinity order obtained in the docking simulations, without covalent-bond formation between both interacting beta-blockers in the best-ranked site. Lastly, experimental ultrasound density and velocity measurements were performed and allowed us to validate and corroborate the computational obtained results
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/24032
UL http://hdl.handle.net/10347/24032
LA eng
NO González-Durruthy, M.; Concu, R.; Vendrame, L.F.O.; Zanella, I.; Ruso, J.M.; Cordeiro, M.N.D.S. Targeting Beta-Blocker Drug–Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study. Molecules 2020, 25, 5425
NO This research was funded by FCT/MCTES through national funds (Michael González-Durruthy, Riccardo Concu, and M. Natália D.S. Cordeiro), grant UID/QUI/50006/2020, as well as by Xunta de Galicia (Juan M. Ruso), grant ED41E2018/08
DS Minerva
RD 3 may 2026