The competition between drugs can be analyzed by molecular modeling and bioinformatics tools. The effect of the displacement of one drug from the complex of the other with human serum albumin (HSA) has been described on the comparison of inhibition constants for the binary and ternary systems. The aim of this work was to determine the competition between amlodipine (AML) and aspirin (ASA) in mulidrug therapy. Binding of AML and ASA can result in decrease or increase of the affinity of the second drug to HSA this can be caused by the location in the same binding site on HSA or by the conformational changes the protein structure. Crystal structure analysis has revealed that HSA consists of a single polypeptide chain of 585 amino acid residues and comprises three structurally homologous domains (I–III): I (residues 1–195), II (196–383), and III (384–585) that assemble to form a heart-shaped molecule. Sub-domain IIA is a high affinity of binding sites for drugs. ASA also known by trade name ASA and AML are used in our work. Autodock4 was carried out to calculate possible interactions between the protein and AML and ASA. The results show interaction of AML and HSA in site II, around the ASP259, ASP255 that the best inhibition constant of protein (Ki) and docking energy are 5.25 μM and -7.2 kcal/mol, respectively. The ASA located in sub-domain IIA around the Lys199 with the best Ki and docking energy are18.51μM and-6.46 kcal/mol. The results indicate that this drugs bind in different sites in sub-domain II with different affinity and obviously we have a ternary system. Our results have been confirmed by spectroscopic analysis.

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