Docking And Molecular Dynamics Simulation Studies Of Insulin-Β-Cyclodextrin Interactions

Muhammad, Erma Fatiha (2016) Docking And Molecular Dynamics Simulation Studies Of Insulin-Β-Cyclodextrin Interactions. Masters thesis, Universiti Sains Malaysia.

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    Abstract

    Interaksi protein-ligan memainkan peranan penting dalam menyediakan produk farmaseutikal yang baharu. Kajian ini merupakan usaha untuk memahami struktur dan dinamik kompleks insulin-siklodekstrin sebagai formula insulin oral yang baharu. Pendokkan dan simulasi dinamik molekul telah dijalankan untuk mengkaji interaksi antara monomer insulin dan dimer insulin terhadap β-siklodekstrins (β-CDs). Kajian pendokkan molekul berganda telah dijalankan menggunakan program Autodock v4.2 untuk menentukan bilangan β-CD yang boleh terikat pada tapak ikatan insulin selain menentukan konformasi insulin-β-CD yang paling stabil. Pendokkan molekul dengan 100 struktur rawak menggunakan konformasi awal nisbah monomer insulin kepada β-CD dan dimer insulin-β-CD 1:1 telah dijalankan dan daripada struktur pendokkan terakhir, β-CD telah ditambah dan proses diulangi sehingga peningkatan tenaga didapati. Keputusan pendokkan molekul menunjukkan maksimum empat molekul β-CD boleh terikat kepada struktur insulin dan nisbah insulin kepada β-CD 1:3 menghasilkan tenaga bebas pengikatan terendah. Selain pembentukan ikatan hidrogen, keputusan pendokkan menunjukkan bahawa interaksi hidrofobik memainkan peranan penting dalam menentukan kestabilan kompleks insulin-β-CD. Protein-ligand interactions play an essential role in the design of new pharmaceutical products. This study attempts to understand the theoretical basis on the structure and dynamics of insulin-cyclodextrin complex for new oral insulin formulation. Docking and molecular dynamics simulations were performed to explore the interactions between insulin monomer and insulin dimer with β-cyclodextrins (β-CDs). A multiple molecular docking study was performed using the Autodock v4.2 program to determine the number of β-CD that can adhere to the binding sites of insulin as well as to determine the most stable conformations of insulin to β-CDs. A 100 random structure docking using 1:1 insulin monomer-β-CD and insulin dimer-β-CD ratio were conducted and from the final docked structure, additional β-CDs were added and the process were repeated until the energy increase. Molecular docking results revealed that a maximum of four β-CDs can bind to an insulin structure with the 1:3 insulin-β-CD ratios having the lowest binding free energy.

    Item Type: Thesis (Masters)
    Subjects: Q Science > QD Chemistry > QD1-999 Chemistry
    Divisions: Pusat Pengajian Sains Kimia (School of Chemistry) > Thesis
    Depositing User: Mr Noorazilan Noordin
    Date Deposited: 16 Jan 2017 16:18
    Last Modified: 12 Apr 2017 11:23
    URI: http://eprints.usm.my/id/eprint/31627

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