在AlphaFold预测的蛋白质结构蛋白质上进行全面的分子对接:识别 puberulic 酸的目标蛋白质候选者
Teppei Hayama1, Rin Sugawara1, Ryo Kamata1
1Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University.
The Journal of toxicological sciences
|July 2, 2025
概括
一个新的计算管道通过选蛋白质组来帮助识别有毒化合物的标. 它确定了 puberulic 酸的潜在脏毒性目标,推进了预测毒理学.
科学领域:
- 计算毒理学计算毒理学
- 蛋白质组学是指蛋白质组学.
- 药物发现 药物发现
背景情况:
- 鉴定有毒化合物的分子标是具有挑战性的,特别是针对非标效应和未知的机制.
- 需要高通量选方法来加快毒理学评估.
研究的目的:
- 开发和验证用于高通量分子对接和丰富分析的计算管道,以识别有毒化合物目标.
- 调查 puberulic 酸的潜在分子点, puberulic 酸是一种与毒性有关的化合物.
主要方法:
- 开发了一个计算管道,将高通量分子对接与AlphaFold2预测的蛋白质组和丰富分析集成在一起.
- 使用已知的药物标对验证了管道,评估了标排名和绑定姿势一致性.
- 将管道应用于 puberulic 酸,以确定人类和小鼠的潜在高亲和度目标.
主要成果:
- 该管道成功地将已知的药物点排名在超过21000个蛋白质的前1.15%内,在验证测试中.
- 在人类和小鼠中确定了/肌化醇共运输体2 (SLC5A11) 作为 puberulic 酸的高亲和性标.
- 对接得分分布独立于蛋白质长度和AlphaFold2信心得分,表明方法的稳定性.
结论:
- 开发的in silico框架有效地识别了有毒物质和治疗药物的潜在分子标.
- 这种工具增强了预测性毒理学,特别是当实验数据稀缺时.
- 这些发现表明, puberulic 酸的毒性可能涉及通过 SLC5A11.11 破坏透调节的.
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