MOLECULAR DOCKING AND MOLECULAR DYNAMIC STUDIES: SCREENING PHYTOCHEMICALS OF Acalypha indica AGAINST BRAF KINASE RECEPTORS FOR POTENTIAL USE IN MELANOCYTIC TUMOURS

Abstract

Melanocytic tumors are a type of cancer that is most commonly found on the skin. The melanoma prevalence rate has risen dramatically over the last 50 years. As a result, the discovery of new therapeutic agents is critical. The BRAF kinase is one of the receptors involved in cell apoptosis. Dabrafenib is a selective BRAF inhibitor with common side effects such as rash, photosensitivity, and hyperkeratosis. Meanwhile, Acalypha indica is a plant that has been widely reported as a source of antiproliferative and proapoptotic compounds. However, the phytochemicals in A. indica that play an important role in melanocytic tumors have yet to be discovered. Molecular docking is a structure-based drug design method that is used to identify potential hits during the drug discovery process. The aims of this study are to obtain candidate lead compounds for BRAF kinase based on binding mode interaction and binding stability by using AutoDock 4.2 and GROMACS 2019.6, respectively, for molecular docking and molecular dynamics (MD). The native ligand, SM5, has estimated free energy of binding and an inhibitory constant of -5.93 kcal/mol and 45.30 µM, respectively. 2-Methyl anthraquinone, chrysin, stigmasterol, and γ-sitosterol have higher binding energy, with an estimated free energy of binding of -6.24, -6.67, -6.35, and -6.14 kcal/mol, respectively. According to the MD simulation, stigmasterol and γ-sitosterol will be more effective at stabilizing the 6XFP complex during 100 ns. Finally, stigmasterol and γ-sitosterol are potential lead compounds as BRAF inhibitors.

Prediction of a Stable Complex of Compounds in the Ethanol Extract of Celery Leaves (Apium graveolens L.) Function as a VKORC1 Antagonist

“…This work is licensed under the Creative Commons Attribution 4.0 International License dynamics simulations, there was a large movement between the protein and the ligand. 10,20 d. MMGBSA MMGBSA is a popular approximation method for estimating the free energy of binding of macromolecules and ligands. 21 The MMGBSA calculation method includes components of van der Waals energy (EVDW), electrostatic energy (EEL), Electrostatic to Solvation Free Energy (EGB), Non-polar to Solvation Free Energy (ESURF), ∆Ggas, ∆Gsolv, and total bond-free energy (∆Gtotals).…”

“…Moreover, computational approaches such as molecular docking simulation and molecular dynamics are adopted mainly to screen potential drugs and molecules from various databases and libraries, saving experimentation costs and time in drug discovery. [9][10][11][12] This research aims to study the affinity, interaction pattern, and stability complex of chemical compounds in celery leaves (Apium graveolens L.) on the structure of the VKORC1 enzyme as a candidate lead compound anticoagulant. We began by searching the literature for plant isolates before moving on to molecular docking and molecular dynamics.…”

Penambatan Molekul dan Dinamika Molekul beberapa Fitokimia dari Acalypha Indica L. sebagai Inhibitor Matriks Metalloproteinase9

“…Untuk menyiapkan model, digunakan kotak simulasi kubik dengan jarak buffer satu mikron. Ion lawan, seperti Na + dan Cl -, dimasukkan ke dalam sistem sampai kondisi netral (untuk detailnya, lihat Asnawi et al 2022) [15]. Tahapan terakhir menggunakan algoritma gmx_MMGBSA dan gmx_MMGBSA_ana untuk menghitung energi ikatan dan kontribusi residu terhadap energi ikatan dalam kompleks [16,17].…”

Screening of Ashitaba (Angelica Keiskei K.) Compounds as Potential Mycobacterium Tuberculosis Kasa Inhibitors

“…The MD simulation was performed in the following order (for more details, see Asnawi et al, 2022) [9,14]: First, each system underwent three stages of energy minimization utilizing the 1000-step steepest descent and 1000-step conjugate gradient algorithms. Using the same method, this was accomplished through protein restraint in the first and second stages and without any restrictions in the third stage.…”

“…The overall drug development process can be sped up by using computational approaches in drug discovery to screen candidate compounds before in vitro cell culture-based assays or chemical kits [8]. The recent application of molecular docking and MD techniques to identify the lead compound from medicinal plants has shown the technique's importance [9,10]. Therefore, this paper aimed to use computational techniques to identify the responsible phytochemicals from Ashitaba (Angelica keiskei K.) in inhibiting the Mycobacterium tuberculosis KasA.…”