Evaluation of the effect of Fluoropyrimidine on HNF۴alphaprotein by molecular docking method

Objective: Fluoropyrimidine is one of the drugs used in chemotherapyfor stomach cancer. Studies show that this drug canaffect the HNF۴alpha protein and reduce the progression ofcancer. In this study, we try to investigate the effect of this drugbinding to the protein HNF۴alpha Investigate the interactionbetween this protein and the drug by molecular dockingMaterial and Methods: In this descriptive-analytical project,we first downloaded the most suitable three-dimensional structureof HNF۴alpha protein in terms of resolution and numberof suitable chains from the Uniprot site in pdb format. We seesome specifications of this protein below. This protein has۵ chains A, C, G, E, I was. resolution =۳.۷۰A Then, proteinchains were examined using Chimera software. The most suitablechain was c chain, which had more amino acids than otherchains, and the largest protein chain was HNF۴alpha. Throughthis software, water molecules and all We removed the solventsfrom this chain and hydrogen ions and charge bar were addedto the chain and finally saved in pdb format HNF۴alpha proteinin the next step, we downloaded the structure of Fluoropyrimidine from Pubcheem site in SDF format. The informationabout Nitidine Chloride was as follows: Molecular formula:C۴H۳FN۲ Molecular weight: ۹۸.۰۸ ۳D Conferm FluoropyrimidineTo perform the docking process, pyrx software was used.In this software, after entering the protein as a receptor and thedrug Fluoropyrimidine as a ligand, we obtained the binding sitethrough the Deepsite, the specifications of which were as follows:Center c= ۲۵.۰۰ Center y=۲۵.۰۰ Center z=۲۵.۰۰Results: After docking with Pyrex software, ۱۰ models weresuggested, the first three models being the best docking modes,the results of which were obtained in the table below modelBinding affinity kcal/mol Rmsd ۱ --۴.۰۰ kcal/mol ۰.۰۰ ۲ -۳.۷kcal/mol ۲.۷۱۳ ۳ -۳.۷ kcal/mol ۱۶.۷۶۹Conclusion: According to Docking results, it can be concludedthat Fluoropyrimidine with poor negative binding energy cannotbind well with HNF۴alpha protein, but there is a proper orientationof the drug within the protein according to RMSD = ۰ and this drugcannot be a good drug. To bind to the HNF۴alpha protein

Keywords:

Fluoropyrimidine , HNF۴alpha , Molecular docking