Simulasi Dinamika Molekul Interaksi Senyawa Demetoksikurkumin dengan Matrix Metalloproteinase-1 untuk Anti Photoaging dan Photocarcinogenesis

Abstract

Radiasi sinar matahari (UV) menyebabkan photoaging dan photocarcinogenesis seperti melanoma melalui aktivasi Matrix metalloproteinase- 1 (MMP-1). MMP-1 adalah endopeptidase ekstraseluler yang aktivitasnya paling banyak dipicu paparan sinar UV dan bertanggung jawab dalam mendegradasi kolagen fibril tipe I dan tipe III pada kulit. Demetoksikurkumin merupakan salah satu polifenol alami kelompok kurkuminoid yang yang berpotensi secara in silico sebagai inhibitor MMP-1 melalui metode penambatan molekul untuk anti photoaging dan photocarcinogenesis. Penelitian bertujuan menguji stabilitas interaksi reseptor-ligan dan mengetahui mekanisme inhibisi senyawa demetoksikurkumin dengan MMP-1 hasil penambatan molekul menggunakan simulasi dinamika molekul. Simulasi MD yang berlangsung selama 10 ns mengindikasikan kestabilan pengikatan demetokskikurkumin pada sisi katalitik dan kantong S1’ MMP-1 dan terjadi stabilisasi struktur MMP-1 berdasarkan nilai RMSD, Rg, SASA, jumlah ikatan hidrogen, RMSF, dan energi ikat MM-PSA.

Sun radiation (UV) causes photoaging and photocarcinogenesis such as melanoma through activation of Matrix metalloproteinase-1 (MMP-1). MMP-1 is an extracellular endopeptidase whose activity is most triggered by UV exposure and is responsible for degrading type I and type III fibril collagen in the skin. Demethoxycurcumin is one of the natural polyphenols of the curcuminoid group that has the potential in silico as MMP-1 inhibitor through the molecular docking method for anti photoaging and photocarcinogenesis. The study aimed to test the stability of receptor-ligand interactions and find out the inhibition mechanism of demetoxycorquine compounds with MMP-1 molecular tether results using molecular dynamics simulations. Md simulations lasting for 10 ns indicate the stability of detoxcuff binding on the catalytic side and pockets of S1' MMP-1 and stabilization of MMP-1 structures based on RMSD, Rg, SASA values, the number of hydrogen bonds, RMSF, and MM-PSA binding energy.