Show simple item record

dc.contributor.authorEvoli, Stefania
dc.contributor.authorMobley, David L.
dc.contributor.authorGuzzi, Rita
dc.contributor.authorRizzuti, Bruno
dc.date.accessioned2017-02-15T08:32:15Z
dc.date.available2017-02-15T08:32:15Z
dc.date.issued2016-11-10
dc.identifier.citationEvoli S, Mobley DL, Guzzi R, Rizzuti B (2016) Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations. Phys Chem Chem Phys 18: 32358–32368. Available: http://dx.doi.org/10.1039/c6cp05680f.
dc.identifier.issn1463-9076
dc.identifier.issn1463-9084
dc.identifier.doi10.1039/c6cp05680f
dc.identifier.urihttp://hdl.handle.net/10754/622898
dc.description.abstractHuman serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow's drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.
dc.description.sponsorshipDLM appreciates financial support from the National Institutes of Health (1R01GM108889-01).
dc.publisherRoyal Society of Chemistry (RSC)
dc.relation.urlhttp://pubs.rsc.org/en/Content/ArticleLanding/2016/CP/C6CP05680F#!divAbstract
dc.relation.urlhttp://europepmc.org/articles/pmc5130592?pdf=render
dc.rightsArchived with thanks to Physical Chemistry Chemical Physics
dc.rightsThis file is an open access version redistributed from: http://europepmc.org/articles/pmc5130592?pdf=render
dc.titleMultiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations
dc.typeArticle
dc.contributor.departmentKAUST Catalysis Center (KCC)
dc.identifier.journalPhys. Chem. Chem. Phys.
dc.rights.embargodate2017-11-10
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Physics, University of Calabria, 87036 Rende, Italy
dc.contributor.institutionDepartments of Pharmaceutical Sciences and Chemistry, University of California, Irvine, USA
dc.contributor.institutionCNISM Unit, University of Calabria, 87036 Rende, Italy
dc.contributor.institutionCNR-NANOTEC, Licryl-UOS Cosenza and CEMIF.Cal, Department of Physics, University of Calabria, 87036 Rende, Italy
kaust.personEvoli, Stefania
refterms.dateFOA2020-06-30T13:00:22Z


Files in this item

Thumbnail
Name:
Articlefile1.pdf
Size:
688.5Kb
Format:
PDF
Description:
Article

This item appears in the following Collection(s)

Show simple item record