Abstract：
Spinocerebellar ataxia (SCA) is a rare neurological illness inherited dominantly that causes severe impairment and premature mortality. While each rare disease may affect individuals infrequently, collectively they pose a significant healthcare challenge. It is mainly carried out due to the expansion of RNA triplet (CAG) repeats, although missense or point mutations can also be induced. Unfortunately, there is no cure; only symptomatic treatments are available. To date, SCA has about 48 subtypes, the most common of these being SCA 1, 2, 3, 6, 7, 12, and 17 having CAG repeats. Using molecular docking and molecular dynamics (MD) simulation, this study seeks to investigate effective natural herbal neuroprotective compounds against CAG repeats, which are therapeutically significant in treating SCA. Initially, virtual screening followed by molecular docking was used to estimate the binding affinity of neuroprotective natural compounds toward CAG repeats. The compound with the highest binding affinity, somniferine, was then chosen for MD simulation. The structural stability, interaction mechanism, and conformational dynamics of CAG repeats and somniferine were investigated via MD simulation. The MD study revealed that during the simulation period, the interaction between CAG repeats and somniferine stabilizes and results in fewer conformational variations. This in silico study suggests that Somniferine can be used as a therapeutic medication against RNA CAG repeats in SCA.
摘要：
脊髓小脑共济失调（SCA）是一种罕见的神经系统疾病，主要遗传，可导致严重损害和过早死亡。虽然每种罕见疾病可能很少影响个体，总的来说，它们构成了重大的医疗保健挑战。它主要是由于RNA三联体（CAG）重复序列的扩展而进行的，虽然错义或点突变也可以诱导。不幸的是,没有治愈方法；只有对症治疗。迄今为止,SCA有大约48个亚型,其中最常见的是具有CAG重复的SCA1、2、3、6、7、12和17。利用分子对接和分子动力学(MD)模拟,这项研究旨在研究有效的天然草药神经保护化合物对CAG重复，在治疗SCA方面具有重要的治疗意义。最初，利用虚拟筛选和分子对接技术评估神经保护性天然化合物对CAG重复序列的结合亲和力.具有最高结合亲和力的化合物，催眠素,然后选择MD模拟。结构稳定性,相互作用机制，并通过MD模拟研究了CAG重复序列和大豆素的构象动力学。MD研究表明，在模拟期间，CAG重复和somniferine之间的相互作用稳定并导致更少的构象变化。这项计算机模拟研究表明，Somniferine可以用作针对SCA中RNACAG重复的治疗药物。
