绘制人体表面的可向部位,用于设计新型结合剂
Petra E M Balbi1, Ahmed Sadek1, Anthony Marchand1
1Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
概括
研究人员在人类细胞表面发现了数千种潜在的药物点. 他们开发了计算方法和实验验证,以设计蛋白质结合剂,加速创建新的向疗法.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 药物发现 药物发现 药物发现
背景情况:
- 人类细胞表面对细胞功能和疾病途径至关重要.
- 准细胞表面蛋白质具有治疗潜力,但由于广大的搜索空间和有限的粘合剂数据,它面临着挑战.
- 新型蛋白质结合剂设计是开发针对细胞表面向药物的未经探索的策略.
研究的目的:
- 系统地分析人类细胞表面,寻找可准的部位.
- 开发和验证设计蛋白质结合剂对细胞表面标的计算和实验方法.
- 为未来的研究创建一个可访问的生成数据数据库.
主要方法:
- 对整个人体表面的系统分析有助于确定可针对性的地点.
- 开发潜在的结合种子,以启动蛋白质设计.
- 在FGFR2,IFNAR2和HER3位上使用蛋白质支架和循环的实验验证.
- 利用机器学习和基于物理的方法进行计算蛋白质设计.
主要成果:
- 在人体表面,大约有4,500个可准的部位被确定.
- 结合种子的成功率很高,是结合剂设计的起点.
- 实验验证证了计算设计方法的实用性.
- 创建了SURFACE-Bind数据库,提供对所有生成数据的开放访问.
结论:
- 计算和实验策略为设计针对人类表面的蛋白质结合剂提供了有效的起点.
- 计算蛋白质设计管道的持续改进是必要的.
- 开发的方法和数据加速了针对人体表面ome.net的向治疗方法的开发.
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