"In Silico Analysis of CD40 Mutations and Their Implications for Quinol" by Luluk Yunaini, Diyah Kristanty et al.
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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Graves' disease is an autoimmune disorder in which the CD40-CD154 interaction plays a critical role in T-cell activation. In this study, in silico methods were employed to analyze the binding interactions of quinoline-benzoic acid derivatives (NSB, FSB, and NQB) with the CD40 receptor and to investigate the implications of specific CD40 mutations for drug efficacy. In this reseach conducted by molecular simulation approach with molecular docking Results Mutation analysis of CD40 identified alterations in key residues, such as R203C, which may impact ligand-independent activation and downstream TRAF binding, crucial for signal transduction. These findings highlight the therapeutic potential of quinoline-benzoic acid derivatives for targeting CD40 in Graves' disease, particularly in the context of receptor mutations. The integration of molecular docking, mutation analysis, and pharmacokinetic profiling provides a comprehensive framework for designing effective CD40-targeted therapies.

Bahasa Abstract

Graves' Disease adalah kelainan autoimun di mana interaksi CD40-CD154 memainkan peran penting dalam aktivasi sel T. Dalam penelitian ini, metode in silico digunakan untuk menganalisis interaksi pengikatan turunan asam kuinolin-benzoat (NSB, FSB, dan NQB) dengan reseptor CD40 dan untuk menyelidiki implikasi mutasi CD40 spesifik terhadap kemanjuran obat. Dalam penelitian ini dilakukan dengan pendekatan simulasi molekuler dengan docking molekul. Hasil Analisis mutasi CD40 mengidentifikasi perubahan pada residu utama, seperti R203C, yang dapat berdampak pada aktivasi independen ligan dan pengikatan TRAF hilir, yang penting untuk transduksi sinyal. Temuan ini menyoroti potensi terapeutik turunan asam kuinolin-benzoat untuk menargetkan CD40 pada penyakit Graves, khususnya dalam konteks mutasi reseptor. Integrasi docking molekuler, analisis mutasi, dan profil farmakokinetik memberikan kerangka kerja komprehensif untuk merancang terapi bertarget CD40 yang efektif.

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