Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents
Background & objectives: the interaction of albumin- the most important plasma protein- with various drugs leads to variations in the pharmacokinetics of drugs. Since interaction of different pharmaceuticals with albumin is determinant in the estimation of dose and prediction of drug-drug and dr...
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| Format: | Article |
| Language: | fas |
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Ardabil University of Medical Sciences
2018-07-01
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| Series: | Journal of Ardabil University of Medical Sciences |
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| Online Access: | http://jarums.arums.ac.ir/browse.php?a_code=A-10-1082-1&slc_lang=en&sid=1 |
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| author | Reza Mamizadeh Nima Razzaghi-Asl |
| author_facet | Reza Mamizadeh Nima Razzaghi-Asl |
| author_sort | Reza Mamizadeh |
| collection | DOAJ |
| description | Background & objectives: the interaction of albumin- the most important plasma protein- with various drugs leads to variations in the pharmacokinetics of drugs. Since interaction of different pharmaceuticals with albumin is determinant in the estimation of dose and prediction of drug-drug and drug-food interferences, studying the binding ability of different drugs with albumin is an active area of research.
Methods: Docking studies were performed by Lamarckian Genetic Algorithm of AutoDock 4.2 program. The three-dimensional structures of albumin were obtained from Brookhaven protein data bank (2BXD & 2BXF; www.rcsb.org). Pre-processing of molecules was done using AM1 method and AutoDock Tools 1.5.4 software. AM1 optimization method was performed using Polak-Ribiere (conjugate gradient) algorithm with termination condition as RMS gradient of 0.1 Kcal/Å mol. Schematic representation of drug-albumin complexes were obtained by Ligplot.
Results: Oxiconazole and fenticonazole were top-ranked drugs in binding to site 1 (subdomain IIA) and 2 (subdomain IIIA) of albumin, respectively (∆Gb -9.01 and -9.89 kcal.mol-1). Leu238 and Ala291 were the key residues of site 1 due to hydrophobic contacts with all of the antifungals, while Ile388, Asn391 and Leu430 were the key residues of site 2. A few structure binding relationship rules could be extracted from the binding pattern of antifungal drugs.
Conclusion: It was found that antifungal agents might have higher affinity toward site 2 of albumin rather than site 1. Estimated high albumin affinities of antifungals provided the possibility of drug-drug or drug-food interactions. It seemed that hydrophobic contacts were more significant in binding antifungals to albumin.
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| first_indexed | 2024-12-23T04:32:19Z |
| format | Article |
| id | doaj.art-3041299282a64dd6bdab57d48284bfe5 |
| institution | Directory Open Access Journal |
| issn | 2228-7280 2228-7299 |
| language | fas |
| last_indexed | 2024-12-23T04:32:19Z |
| publishDate | 2018-07-01 |
| publisher | Ardabil University of Medical Sciences |
| record_format | Article |
| series | Journal of Ardabil University of Medical Sciences |
| spelling | doaj.art-3041299282a64dd6bdab57d48284bfe52022-12-21T17:59:59ZfasArdabil University of Medical SciencesJournal of Ardabil University of Medical Sciences2228-72802228-72992018-07-01182173190Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal AgentsReza Mamizadeh0Nima Razzaghi-Asl1 Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran Background & objectives: the interaction of albumin- the most important plasma protein- with various drugs leads to variations in the pharmacokinetics of drugs. Since interaction of different pharmaceuticals with albumin is determinant in the estimation of dose and prediction of drug-drug and drug-food interferences, studying the binding ability of different drugs with albumin is an active area of research. Methods: Docking studies were performed by Lamarckian Genetic Algorithm of AutoDock 4.2 program. The three-dimensional structures of albumin were obtained from Brookhaven protein data bank (2BXD & 2BXF; www.rcsb.org). Pre-processing of molecules was done using AM1 method and AutoDock Tools 1.5.4 software. AM1 optimization method was performed using Polak-Ribiere (conjugate gradient) algorithm with termination condition as RMS gradient of 0.1 Kcal/Å mol. Schematic representation of drug-albumin complexes were obtained by Ligplot. Results: Oxiconazole and fenticonazole were top-ranked drugs in binding to site 1 (subdomain IIA) and 2 (subdomain IIIA) of albumin, respectively (∆Gb -9.01 and -9.89 kcal.mol-1). Leu238 and Ala291 were the key residues of site 1 due to hydrophobic contacts with all of the antifungals, while Ile388, Asn391 and Leu430 were the key residues of site 2. A few structure binding relationship rules could be extracted from the binding pattern of antifungal drugs. Conclusion: It was found that antifungal agents might have higher affinity toward site 2 of albumin rather than site 1. Estimated high albumin affinities of antifungals provided the possibility of drug-drug or drug-food interactions. It seemed that hydrophobic contacts were more significant in binding antifungals to albumin. http://jarums.arums.ac.ir/browse.php?a_code=A-10-1082-1&slc_lang=en&sid=1Drug Antifungal Albumin Pharmacokinetics Molecular Docking |
| spellingShingle | Reza Mamizadeh Nima Razzaghi-Asl Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents Journal of Ardabil University of Medical Sciences Drug Antifungal Albumin Pharmacokinetics Molecular Docking |
| title | Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents |
| title_full | Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents |
| title_fullStr | Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents |
| title_full_unstemmed | Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents |
| title_short | Molecular Modeling of Drug-Albumin Interactions: A case Study on Antifungal Agents |
| title_sort | molecular modeling of drug albumin interactions a case study on antifungal agents |
| topic | Drug Antifungal Albumin Pharmacokinetics Molecular Docking |
| url | http://jarums.arums.ac.ir/browse.php?a_code=A-10-1082-1&slc_lang=en&sid=1 |
| work_keys_str_mv | AT rezamamizadeh molecularmodelingofdrugalbumininteractionsacasestudyonantifungalagents AT nimarazzaghiasl molecularmodelingofdrugalbumininteractionsacasestudyonantifungalagents |