A Molecular Dynamics approach to ligand-receptor interaction in the Aspirin-Human Serum Albumin complex

H. ARIEL ALVAREZ; ANDRÉS N. MCCARTHY; J. RAÚL GRIGERA

Journal of Biophysics

Hindawi Publishing Corporation

Año: 2012 vol. 2012 p. 1 - 7

1687-8000

In this work we present a study of the interaction between Human Serum Albumin (HSA) andAcetyl Salicylic Acid (ASA - C9H8O4) by Molecular Dynamics simulations (MD). Starting from anexperimentally resolved structure of the complex, we performed the extraction of the ligand bymeans of the application of an external force. After stabilization of the system, we quantified theforce used to remove the ASA from its specific site of binding to HSA and calculated themechanical non-equilibrium external work done during this process. We obtain a reasonable valuefor the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamicpotential) between the complexed and non complexed states. To achieve this goal, we used thefinite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluatethe effect of the solvent, we calculated the so called `viscous work´, i.e. the work done to move theaspirin in the same trajectory through the solvent in absence of the protein, so as to assess therelevance of its contribution to the total work. The results are in good agreement with the availableexperimental data for the Albumin affinity constant for Aspirin, obtained through quenchingfluorescence methods.Journal of BiophysicsVolume 2012 (2012), Article ID 642745, 7 pagesdoi:10.1155/2012/642745