scholarly journals Steric and Allosteric Effects of Fatty Acids on the Binding of Warfarin to Human Serum Albumin Revealed by Molecular Dynamics and Free Energy Calculations

2011 ◽  
Vol 59 (7) ◽  
pp. 860-867 ◽  
Author(s):  
Shin-ichi Fujiwara ◽  
Takashi Amisaki
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Free Energy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Free Energy Calculations ◽  
Energy Calculations

scholarly journals Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

2016 ◽  
Author(s):  
Stefania Evoli ◽  
David L. Mobley ◽  
Rita Guzzi ◽  
Bruno Rizzuti
Keyword(s):  
Free Energy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Sites ◽  
Free Energy Calculations ◽  
Binding Modes ◽  
Energy Calculations ◽  
Multiple Binding Sites ◽  
Multiple Binding

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.Graphical abstractFocusAlchemical free energy methods can identify favored binding modes of a ligand within a large protein with multiple binding sitesHighlightsHuman serum albumin binds the anti-inflammatory drug ibuprofen in multiple sitesAlchemical free energy calculations predicted favored binding modes of ibuprofenBound geometry, affinity and protonation state of the ligand were determinedSimulations identified a number of previously undetected binding sites for ibuprofenFree energy methods can be used to study large proteins with multiple binding sites

scholarly journals Characterization of the Solution Structure of Human Serum Albumin Loaded with a Metal Porphyrin and Fatty Acids

2011 ◽  
Vol 100 (9) ◽  
pp. 2293-2301 ◽  
Author(s):  
Matthias J.N. Junk ◽  
Hans W. Spiess ◽  
Dariush Hinderberger
Keyword(s):  
Fatty Acids ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Solution Structure ◽  
Metal Porphyrin

scholarly journals A Comprehensive Spectroscopic Analysis of the Ibuprofen Binding with Human Serum Albumin, Part II

2021 ◽  
Vol 89 (3) ◽  
pp. 30
Author(s):  
Anna Ploch-Jankowska ◽  
Danuta Pentak ◽  
Jacek E. Nycz
Keyword(s):  
Fatty Acids ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Tertiary Structure ◽  
Temperature Characteristic ◽  
The Body ◽  
Structural Modifications ◽  
Influence Of Temperature On ◽  
Exogenous Substances

Human serum albumin (HSA) is the most abundant human plasma protein. HSA plays a crucial role in many binding endos- and exogenous substances, which affects their pharmacological effect. The innovative aspect of the study is not only the interaction of fatted (HSA) and defatted (dHSA) human serum albumin with ibuprofen (IBU), but the analysis of the influence of temperature on the structural modifications of albumin and the interaction between the drug and proteins from the temperature characteristic of near hypothermia (308 K) to the temperature reflecting inflammation in the body (312 K and 314 K). Ibuprofen is a non-steroidal anti-inflammatory drug. IBU is used to relieve acute pain, inflammation, and fever. To determine ibuprofen’s binding site in the tertiary structure of HSA and dHSA, fluorescence spectroscopy was used. On its basis, the fluorescent emissive spectra of albumin (5 × 10−6 mol/dm3) without and with the presence of ibuprofen (1 × 10−5–1 × 10−4 mol/dm3) was recorded. The IBU-HSA complex’s fluorescence was excited by radiation of wavelengths of λex 275 nm and λex 295 nm. Spectrophotometric spectroscopy allowed for recording the absorbance spectra (zero-order and second derivative absorption spectra) of HSA and dHSA under the influence of ibuprofen (1 × 10−4 mol/dm3). To characterize the changes of albumin structure the presence of IBU, circular dichroism was used. The data obtained show that the presence of fatty acids and human serum albumin temperature influences the strength and type of interaction between serum albumin and drug. Ibuprofen binds more strongly to defatted human serum albumin than to albumin in the presence of fatty acids. Additionally, stronger complexes are formed with increasing temperatures. The competitive binding of ibuprofen and fatty acids to albumin may influence the concentration of free drug fraction and thus its therapeutic effect.

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