{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:53:06Z","timestamp":1776819186375,"version":"3.51.2"},"reference-count":78,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED41E2018\/08"],"award-info":[{"award-number":["ED41E2018\/08"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this work, one of the most prevalent polypharmacology drug\u2013drug interaction events that occurs between two widely used beta-blocker drugs\u2014i.e., acebutolol and propranolol\u2014with 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\u2013drug interactions. Furthermore, the total affinity for the stabilization of the drug\u2013drug 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\u2013drug 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.<\/jats:p>","DOI":"10.3390\/molecules25225425","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T10:46:26Z","timestamp":1605782786000},"page":"5425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeting Beta-Blocker Drug\u2013Drug Interactions with Fibrinogen Blood Plasma Protein: A Computational and Experimental Study"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7061-0811","authenticated-orcid":false,"given":"Michael","family":"Gonz\u00e1lez-Durruthy","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"},{"name":"Soft Matter and Molecular Biophysics Group, Department of Applied Physics, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0301-9407","authenticated-orcid":false,"given":"Riccardo","family":"Concu","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-7235","authenticated-orcid":false,"given":"Laura F. Osmari","family":"Vendrame","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Nanoscience, Franciscana University (UFN), Santa Maria 97010-032, RS, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7067-5519","authenticated-orcid":false,"given":"Ivana","family":"Zanella","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Nanoscience, Franciscana University (UFN), Santa Maria 97010-032, RS, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-6754","authenticated-orcid":false,"given":"Juan M.","family":"Ruso","sequence":"additional","affiliation":[{"name":"Soft Matter and Molecular Biophysics Group, Department of Applied Physics, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-8670","authenticated-orcid":false,"given":"M. Nat\u00e1lia D. S.","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/cpt.1434","article-title":"Pharmacodynamic drug\u2013drug interactions","volume":"105","author":"Niu","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_2","first-page":"297","article-title":"Systems approaches to polypharmacology and drug discovery","volume":"13","author":"Boran","year":"2010","journal-title":"Curr. Opin. Drug Discov. Devel."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.tips.2009.07.004","article-title":"Conciliating binding efficiency and polypharmacology","volume":"30","author":"Mestres","year":"2009","journal-title":"Trends Pharmacol. 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