Abstract：
A rare metabolic condition called alkaptonuria (AKU) is caused by a decrease in homogentisate 1,2 dioxygenase (HGO) activity due to a mutation in homogentisate dioxygenase (HGD) gene. Homogentisic acid is a byproduct of the catabolism of tyrosine and phenylalanine that darkens the urine and accumulates in connective tissues which causes an agonizing arthritis. Employing the use of deep learning artificial intelligence (AI) drug design, this study aims to alleviate the current toxicity of the AKU drugs currently in use, particularly nitisinone, by utilizing the natural flavanol kaempferol molecule as a 4-hydroxyphenylpyruvate dioxygenase inhibitor. Kaempferol was employed to generate three effective de novo drug candidates targeting the enzyme 4-hydroxyphenylpyruvate dioxygenase using an AI drug design tool. We present novel AIK formulations in the present study. The AIK\'s (Artificial Intelligence Kaempferol) examination of drug-likeliness among the three led to its choice as a possible target. The toxicity assessment research of AIK demonstrates that it is not only safer to use than other treatments, but also more efficient. The docking of the AIGT with 4-hydroxyphenylpyruvate dioxygenase, which revealed a binding affinity of around -9.099 kcal/mol, highlights the AIK\'s potential as a therapeutic candidate. An innovative approach to deal with challenging circumstances is thus presented in this study by new formulations kaempferol that have been meticulously designed by AI. The results of the in vitro tests must be confirmed in vivo, even though AI-designed AIK is effective and sufficiently safe as computed.
摘要：
一种罕见的代谢疾病称为alkaptonuria（AKU），是由于匀浆双加氧酶（HGD）基因的突变而导致的匀浆1,2双加氧酶（HGO）活性降低所致。均质酸是酪氨酸和苯丙氨酸分解代谢的副产物,其使尿液变黑并积聚在结缔组织中,从而引起激动性关节炎。采用深度学习人工智能（AI）药物设计，这项研究旨在减轻目前使用的AKU药物的毒性，尤其是尼替辛酮,通过利用天然黄烷醇山奈酚分子作为4-羟基苯基丙酮酸双加氧酶抑制剂。使用AI药物设计工具，将山奈酚用于产生三种有效的靶向4-羟基苯丙酮酸双加氧酶的从头药物候选物。我们在本研究中提出了新的AIK制剂。AIK（人工智能Kaempferol）对这三者的药物可能性进行了检查，从而将其选择为可能的目标。AIK的毒性评估研究表明，它不仅比其他治疗方法更安全，而且效率更高。AIGT与4-羟基苯基丙酮酸双加氧酶的对接，其显示约-9.099kcal/mol的结合亲和力，突出了AIK作为治疗候选药物的潜力。因此，在这项研究中，通过AI精心设计的新配方山奈酚提出了一种应对挑战环境的创新方法。体外试验的结果必须在体内确认，即使AI设计的AIK在计算时是有效且足够安全的。
