Study of Human Albumin Protein Interaction with Fluorouracil Anticancer Drug Using Molecular Docking Method

Abstract

Introduction: Drugs are mainly delivered to the target tissues by plasma proteins, such as human serum albumin, in the human body. Practical information about the thermodynamic parameters of drugs and their stability can be obtained using simulation methods, such as molecular docking. Material & Methods: This study, investigated the molecular docking of human serum albumin with fluorouracil anticancer drug. Moreover, partial charges on serum albumin protein atoms and fluorouracil atoms were calculated in this study. The best configuration was also searched using the Lamarckian genetic algorithm. The dimensions of the grid maps were selected to be about 40 * 40 * 40 angstroms with a distance of 0.375 angstroms. The number of genetic algorithms and the number of studies were adjusted to about 100 and 2.5 million, respectively. In the end, the best performed interaction configurations with the least amount of free energy were selected. Ligplot and VMD graphic software were used to view the performed docking. Findings: In the best model, fluorouracil is able to bind to the human serum albumin protein HSA four hydrogen bonds via nitrogen and oxygen atoms with two amino acids tyrosine, one amino acid histidine and one amino acid arginine. The estimation of the free bond energies (kcal/mol) for the best model was -5.1. Negative Gibbs free energy values (ΔG °) indicated a spontaneous process, and a constant binding value (Ka ≈ 109 L • mol-1) demonstrated the optimal biological distribution of the drug in the blood plasma. Discussion & Conclusion: The docking study of the proposed models shows that fluorouracil has an aliphatic ring and hydrophobic fractions and therefore it has a high ability to form hydrophobic interactions with major amino acids at the active site of serum albumin protein.

Keywords

• anti-cancer drug
• binding constant
• fluorouracil
• gibbs free energy
• human serum albumin