مطالعه پتانسيل كامل و داكينگ مولكولي برهم كنش داروهاي ضدسرطان با نانوذره طلا

Full Potential Study and Molecular Docking Interaction of Anticancer Drugs with Au Nanoparticle

در ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ، اﺑﺘﺪا ﺳﺎﺧﺘﺎر ﺳﻪ داروي راﯾﺞ ﺿﺪﺳﺮﻃﺎن ﺷﺎﻣﻞ 6- ﺗﯿﻮﮔﻮاﻧﯿﻦ (6-TG)، ﻫﯿﺪروﮐﺴﯽاوره (NH) و ﺑﻮﺳﻮﻟﻔﺎن ﺑﺎ اﺳﺘﻔﺎده از ﻣﺤﺎﺳﺒﺎت ﮐﻮاﻧﺘﻮﻣﯽ ﺑﻬﯿﻨﻪ و اﻧﺮژي ﺳﺎﺧﺘﺎر ﺑﻬﯿﻨﻪﺷﺪه ﺑﻪ دﺳﺖ آﻣﺪ. ﻫﻤﭽﻨﯿﻦ ﺑﻬﯿﻨﻪﺳﺎزي ﺳﺎﺧﺘﺎر ﻧﺎﻧﻮذره ﻃﻼ ﻧﯿﺰ ﻣﻮرد ﺑﺮرﺳﯽ ﻗﺮار ﮔﺮﻓﺘﻪ اﺳﺖ. در ﻧﻬﺎﯾﺖ ﺑﻪﻣﻨﻈﻮر ﺑﺮرﺳﯽ ﭼﮕﻮﻧﮕﯽ ﺑﺮﻫﻢﮐﻨﺶ داروﻫﺎ ﺑﺎ ﻧﺎﻧﻮذره، ﻣﮑﺎنﻫﺎي ﻣﺨﺘﻠﻒ ﺑﺮﻫﻢﮐﻨﺶ دارو ﺑﺎ ﻧﺎﻧﻮذره ﻣﺤﺎﺳﺒﻪ ﺷﺪ و ﭘﺎﯾﺪارﺗﺮﯾﻦ ﺳﺎﺧﺘﺎر ﺑﻪﻣﻨﻈﻮر ﻣﻄﺎﻟﻌﻪ ﺑﯿﺸﺘﺮ اﻧﺘﺨﺎب ﺷﺪ. اﯾﻦ ﻣﺤﺎﺳﺒﺎت ﺑﺎ اﺳﺘﻔﺎده از FHI-aims، ﮐﻪ ﯾﮏ ﺑﺴﺘﻪ ﻧﺮماﻓﺰاري ﺑﺮ ﭘﺎﯾﻪ ﻧﻈﺮﯾﻪ ﺗﺎﺑﻌﯽ ﭼﮕﺎﻟﯽ ﺗﻮﺳﻌﻪ ﯾﺎﻓﺘﻪ اﺳﺖ، اﻧﺠﺎم ﺷﺪهاﻧﺪ. ﻃﻮل ﭘﯿﻮﻧﺪ و ﺑﻬﺘﺮﯾﻦ اﻧﺮژي ﺑﺮﻫﻢﮐﻨﺶ در اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﮔﺰارش ﺷﺪه اﺳﺖ. ﺑﻪﻣﻨﻈﻮر ﺑﺮرﺳﯽ ﺑﻬﺘﺮ ﻣﮑﺎن ﺑﺮﻫﻢﮐﻨﺶ، ﻧﻮع اورﺑﯿﺘﺎلﻫﺎي درﮔﯿﺮ و ﺷﮑﻞ آﻧﻬﺎ ﻧﯿﺰ ﻧﺸﺎن داده ﺷﺪه اﺳﺖ. ﺑﺮرﺳﯽ اﻧﺮژي ﮔﺎف ﻧﺸﺎن داد ﮐﻤﺘﺮﯾﻦ اﻧﺮژي ﻣﺮﺑﻮط ﺑﻪ ﮐﻤﭙﻠﮑﺲ ﻧﺎﻧﻮذره ﻃﻼ ﺑﺎ داروي 6- ﺗﯿﻮﮔﻮاﻧﯿﻦ اﺳﺖ ﮐﻪ ﺗﺎﯾﯿﺪﮐﻨﻨﺪه ﭘﺎﯾﺪاري ﺷﯿﻤﯿﺎﯾﯽ اﯾﻦ دارو ﺑﺎ ﻧﺎﻧﻮذره اﺳﺖ. ﺑﺮرﺳﯽﻫﺎ ﻧﺸﺎن داد ﮐﻪ اﻧﺮژي اﺗﺼﺎل ﻧﺎﻧﻮذره ﻃﻼ ﺑﺎ داروﻫﺎ ﺑﻪ ﺗﺮﺗﯿﺐ ﺑﻮﺳﻮﻟﻔﺎن، ﻫﯿﺪروﮐﺴﯽاوره، 6- ﺗﯿﻮﮔﻮاﻧﯿﻦ اﺳﺖ. ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ اﯾﻦ ﻣﻄﺎﻟﻌﺎت، ﻣﯽﺗﻮان ﻧﺘﯿﺠﻪ ﮔﺮﻓﺖ ﮐﻪ ﻧﺎﻧﻮذرات ﻃﻼ ﻣﯽﺗﻮاﻧﻨﺪ ﺑﻪﻋﻨﻮان ﺣﺎﻣﻞ داروﻫﺎي ﺿﺪﺳﺮﻃﺎن اﺳﺘﻔﺎده ﺷﻮﻧﺪ. ﺳﭙﺲ دارو و ﻧﺎﻧﻮذره ﻃﻼ در ﭘﺎﯾﺪارﺗﺮﯾﻦ ﺣﺎﻟﺖ ﻣﻤﮑﻦ، ﺑﻪﺻﻮرت ﺗﮏﺗﮏ ﺑﺎ ﻧﺮماﻓﺰار Hex 8 ﺑﻪ ﺳﺮم آﻟﺒﻮﻣﯿﻦ اﻧﺴﺎﻧﯽ ﺑﻪﻋﻨﻮان ﮔﯿﺮﻧﺪه، داك ﺷﺪﻧﺪ و در ﻧﻬﺎﯾﺖ اﻧﺮژيﻫﺎي اﺗﺼﺎﻟﯽ و ﺳﺎﯾﺮ ﺑﺮﻫﻢﮐﻨﺶﻫﺎ از ﺟﻤﻠﻪ اﻧﺮژيﻫﺎي اﻟﮑﺘﺮواﺳﺘﺎﺗﯿﮏ، واﻧﺪرواﻟﺴﯽ و ﭘﯿﻮﻧﺪﻫﺎي ﻫﯿﺪروژﻧﯽ ﺑﯿﻦ ﺳﺮم آﻟﺒﻮﻣﯿﻦ اﻧﺴﺎﻧﯽ و داروﻫﺎ ﺑﻪ ﻫﻤﺮاه ﻧﺎﻧﻮذره ﻃﻼ ﻣﺤﺎﺳﺒﻪ ﺷﺪﻧﺪ. ﻣﺸﺨﺺ ﺷﺪ ﮐﻪ ﺟﺎﯾﮕﺎه ﻓﻌﺎل داكﺷﺪه ﺑﺮاي دو داروي ﺑﻮﺳﻮﻟﻔﺎن و 6- ﺗﯿﻮﮔﻮاﻧﯿﻦ ﯾﮑﺴﺎن و ﺑﺮاي داروي ﻫﯿﺪروﮐﺴﯽاوره ﻣﺘﻔﺎوت اﺳﺖ.

In the present study, the structure of three common anticancer drugs including 6-thioguanine (6-TG), hydroxyurea (NH), and busulfan were optimized using quantum computational and obtained minimum energy for them. Also, optimization structure of gold nanoparticle was investigated by density functional theory (DFT). Finally, the binding energy of Au nanoparticle was calculated with the optimized structures of drugs. All different sites of drugs that can be interacted with nanoparticle were considered and the most stable structure was chosen for further study. These calculations were performed using FHI-aims which is a software package based on DFT. The bond length and the best interaction energy were reported in this study. To better investigation of the location of the interaction, the type of orbitals involved in the interaction and their shapes are shown. Gap energy analysis showed that the lowest energy was related to the complex of gold nanoparticle with 6-thioguanine, which confirms the chemical stability of this drug with nanoparticle. Investigations depicted that the binding energy of gold nanoparticle with drugs is busulfan>hydroxyurea>6-thioguanine. Based on these studies, it can be concluded that gold nanoparticle can be used as carriers of anticancer drugs. Au nanoparticle as an anticancer drug deliver was studied with the molecular docking calculations. The human serum albumin (HSA) binding with three anticancer drugs was docked individually with Hex. 8 software and their active sites of interaction were shown as well as. Finally, the binding energies and types of interactions such as electrostatic, van der Waals and hydrogen bonds between HSA and Au@ drugs were presented, clearly. Results showed that the docked active site was obtained for the two drugs, busulfan and thioguanine are the same but it is different for the hydroxyurea drug.