A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex

In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C9H8O 4) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the applicati...

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Detalles Bibliográficos
Autores principales: Álvarez, Hugo Ariel, McCarthy, Andrés Norman, Grigera, José Raúl
Formato: Articulo
Lenguaje:Inglés
Publicado: 2012
Materias:
Biología
human serum albumin
acetylsalicylic acid
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83618
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-83618
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
human serum albumin
acetylsalicylic acid
spellingShingle Biología
human serum albumin
acetylsalicylic acid
Álvarez, Hugo Ariel
McCarthy, Andrés Norman
Grigera, José Raúl
A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
topic_facet Biología
human serum albumin
acetylsalicylic acid
description In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C9H8O 4) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential) between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called "viscous work," that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods.
format Articulo
Articulo
author Álvarez, Hugo Ariel
McCarthy, Andrés Norman
Grigera, José Raúl
author_facet Álvarez, Hugo Ariel
McCarthy, Andrés Norman
Grigera, José Raúl
author_sort Álvarez, Hugo Ariel
title A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
title_short A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
title_full A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
title_fullStr A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
title_full_unstemmed A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
title_sort molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex
publishDate 2012
url http://sedici.unlp.edu.ar/handle/10915/83618
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