A Molecular Dynamics study of the interaction of Acetylsalicylic Acid with HSA mutants K199M and K199A

A. ALVAREZ; ANDRÉS N. MCCARTHY; J. RAÚL GRIGERA

Salta - Argentina

Congreso; 3rd Latin American Protein Society Meeting - XXXIX Reunión Anual de la Sociedad Argentina de Biofísica; 2010

Sociedad Argentina de Biofísica

We present a study of the interaction between Human Serum Albumin (HSA) with amino acid substitutions K199M and K199A and acetylsalicylic acid (ASA) by means of Molecular Dynamics simulations (MD). Starting from a structure obtained from the Protein Data Bank (PDB Id: 2I30), we made the substitution of the polar and charged Lysine199 residue, which is the responsible of the enzymatic action of HSA on ASA1, for the non-polar and neutral aminoacids Alanine and Methionine. Using the COM Pulling tool from GROMACS package, which simulates the action of an external force on the centre of mass of a molecule, we calculate the mechanical Work done during the process of removing the ligand from the site of binding, and compare it with the value obtained for the Complex without the mutations, utilizing the finite sampling correction to the Jarzynski Equality2. These results are in accordance with available experimental data3, validating this computational approach to the study of protein ligand interactions.   References: [1]  F. Yang, C. Bian, L.  Zhu, G. Zhao, Z. Huang, M. Huang, J.Struct.Biol., 2007, v157, 348-355. [2]  C. Jarzynski, Phys. Rev. E., 1997, v56, Number 5, 5018 - 5035. [3] B. Bojko, A. Sułkowska, M. Maciążek, J. Równicka, F. Njau, W.W. Sułkowski, International Journal of Biological Macromolecules, 2008, v42, Number 4, 314-323.