Studi Interaksi Molekuler Ligan Kapsaisinoid terhadap Potensi Kepedasan

Fuadi, Muhammad Dzikri (2025) Studi Interaksi Molekuler Ligan Kapsaisinoid terhadap Potensi Kepedasan. Other thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Penelitian ini menggunakan pendekatan komputasi untuk menganalisis interaksi molekuler antara ligan kapsaisinoid dan reseptor TRPV1 melalui teknik molecular docking. Fokus utama penelitian ini adalah menganalisis pengaruh variasi rantai asil kapsaisinoid terhadap energi ikat ligan pada reseptor TRPV1. Penelitian ini menguji 14 ligan dari kelompok kapsaisinoid, termasuk kapsaisin, beberapa turunannya, serta kapsaisinoid rancangan yang diprediksi memiliki potensi kepedasan tinggi. Nilai potensi kepedasan kapsaisinoid berdasarkan pada data dari penelitian ilmiah. Geometri ligan dioptimasi menggunakan metode dan basis set B3LYP/6-311G melalui aplikasi Orca. Struktur reseptor dipreparasi menggunakan aplikasi Molecular Operating Environment (MOE). Proses docking dilakukan menggunakan aplikasi AutoDock dan AutoDockTools untuk memprediksi energi ikat dan residu pengikatan ligan pada reseptor. Hasil analisis korelasi menunjukkan energi ikat cenderung semakin bernilai negatif (semakin kuat) seiring dengan meningkatnya potensi kepedasan kapsaisinoid, dengan koefisien korelasi sebesar -0,74. Contohnya, berdasarkan hasil docking, energi ikat yang lebih negatif (-9,36 kkal/mol) memiliki potensi kepedasan yang lebih tinggi (8,049), sedangkan energi ikat yang kurang negatif (-6,29 kkal/mol) memiliki potensi kepedasan yang lebih rendah (6,770). Energi ikat dipengaruhi oleh faktor-faktor struktural dari variasi rantai asil kapsaisinoid, seperti jumlah dan posisi ikatan rangkap, panjang rantai, dan percabangan metil. Ligan dengan jumlah ikatan rangkap tertentu meningkatkan enegi ikat karena kerapatan elektron yang tinggi sehingga lebih reaktif, namun kelebihan jumlah ikatan rangkap dapat menurunkan energi ikat karena fleksibilitas ligan yang berkurang. Posisi ikatan rangkap yang strategis meningkatkan energi ikat melalui potensial elektrostatik yang tinggi. Perpanjangan rantai asil meningkatkan energi ikat melalui interaksi hidrofobik, namun perpanjangan rantai asil pada kondisi tertentu menyebabkan hambatan sterik yang menurunkan energi ikat. Percabangan metil meningkatkan energi ikat melalui interaksi hidrofobik. Analisis residu pengikatan menunjukkan bahwa interaksi utama secara umum melibatkan residu Tyr511 dan/atau Thr550 dengan berikatan hidrogen pada gugus amida ligan. Hasil penelitian ini dapat menjadi referensi dalam pengembangan obat baru berbasis kapsaisinoid, dengan aplikasi pada berbagai kondisi yang melibatkan mekanisme reseptor TRPV1, seperti sebagai terapi topikal nyeri neuropatik.
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This study uses a computational approach to analyze the molecular interactions between capsaicinoid ligands and TRPV1 receptors through molecular docking techniques. The main focus of this study is to analyze the effect of capsaicinoid acyl chain variations on the binding energy of ligands on the TRPV1 receptor. This study tested 14 ligands from the capsaicinoid group, including capsaicin, several of its derivatives, and designed capsaicinoids that are predicted to have high pungency potency. The pungency potency value of capsaicinoids is based on data from scientific research. The ligand geometry was optimized using the B3LYP/6- 311G method and basis set through the Orca application. The receptor structure was prepared using the Molecular Operating Environment (MOE) application. The docking process was carried out using the AutoDock and AutoDockTools applications to predict the binding energy and ligand binding residues on the receptor. The results of the correlation analysis showed that the binding energy tended to be increasingly negative (stronger) along with the increasing pungency potency of capsaicinoid, with a correlation coefficient of -0.74. For example, based on the docking results, a more negative binding energy (-9.36 kcal/mol) has a higher pungency potency (8.049), while a less negative binding energy (-6.29 kcal/mol) has a lower pungency potency (6.770). The binding energy is influenced by structural factors of the capsaicinoid acyl chain variation, such as the number and position of double bonds, chain length, and methyl branching. Ligands with a certain number of double bonds increase the binding energy due to their high electron density so they are more reactive, but an excess number of double bonds can decrease the binding energy due to reduced ligand flexibility. The strategic position of the double bond increases the binding energy through high electrostatic potential. The elongation of the acyl chain increases the binding energy through hydrophobic interactions, but the elongation of the acyl chain under certain conditions causes steric hindrance which decreases
the binding energy. Methyl branching increases the binding energy through hydrophobic interactions. Analysis of binding residues showed that the main interactions generally involve residues Tyr511 and/or Thr550 with hydrogen bonds to the amide group of the ligand. The results of this study can be a reference in the development of new capsaicinoid-based drugs, with applications in various co

Item Type:	Thesis (Other)
Uncontrolled Keywords:	B3LYP/6-311G, Kapsaisinoid, Molecular Docking, Potensi Kepedasan, Reseptor TRPV1, Capsaicinoids, Molecular Docking, Pungency Potenc
Subjects:	Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47201-(S1) Undergraduate Thesis
Depositing User:	Muhammad Dzikri Fuadi
Date Deposited:	04 Feb 2025 07:50
Last Modified:	04 Feb 2025 07:50
URI:	http://repository.its.ac.id/id/eprint/117978

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