Kumari Priyanka, Som Anup
Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj - 211002, India.
Bioinformation. 2021 Aug 31;17(8):721-726. doi: 10.6026/97320630017721. eCollection 2021.
Riboswitch, a bacterial regulatory RNA consists of an aptamer (specific ligand binding unit) and an expression platform (gene expression modulation unit), which act as a potential drug target as it regulates critical genes. Therefore, it is of interest to glean information on the binding of c-di-GMP ligand to mutated conserved G20 and C92 residues of cyclic diguanosine monophosphate I (c-di-GMP I) riboswitch using molecular dynamics simulation. The result shows that the binding energy of wild/native type riboswitch-ligand complex (3IRW) is lower than the mutant complexes suggesting that the binding affinity for c-di-GMP ligand decreases in case of mutant riboswitches. The hydrogen bonding interactions analysis also showed a high number of hydrogen bonds formation in the wild type riboswitch-ligand complex as compared to the mutant complexes illustrating stronger interaction of ligand to wild type riboswitch than the mutants. The simulation result shows that the mutations affected riboswitch-ligand interactions. The residues G14, G21, C46, A47, and U92 were identified as the key residues which contributed effectively to the binding of c-di-GMP I riboswitch with the natural ligand.
核糖开关是一种细菌调节RNA，由适体（特异性配体结合单元）和表达平台（基因表达调节单元）组成，由于其调节关键基因，因此可作为潜在的药物靶点。因此，利用分子动力学模拟来收集环二鸟苷单磷酸I（c-di-GMP I）核糖开关的保守G20和C92残基突变后与c-di-GMP配体结合的信息很有意义。结果表明，野生型/天然型核糖开关-配体复合物（3IRW）的结合能低于突变体复合物，这表明突变型核糖开关对c-di-GMP配体的结合亲和力降低。氢键相互作用分析还表明，与突变体复合物相比，野生型核糖开关-配体复合物中形成的氢键数量更多，说明配体与野生型核糖开关的相互作用比与突变体的更强。模拟结果表明，突变影响了核糖开关-配体的相互作用。残基G14、G21、C46、A47和U92被确定为对c-di-GMP I核糖开关与天然配体结合有有效贡献的关键残基。
