连接体B因子指数:在对接中优先考虑蛋白质-连接体复合物的指标
Liliana Halip1, Cristian Neanu1, Sorin Avram1
1Department of Computational Chemistry, "Coriolan Drăgulescu" Institute of Chemistry Timișoara, Romanian Academy, Timișoara, Romania.
Molecular informatics
|September 11, 2025
概括
一个新的指标,联体B因子指数 (LBI),通过比较原子位移来优先考虑对接的蛋白质-联体复合体. LBI与结合亲和力具有中等的相关性,并改善了重制成功,有助于药物发现.
科学领域:
- 计算化学是一种计算化学.
- 化学信息学 化学信息学
- 药物发现 药物发现
背景情况:
- 对接是早期药物发现中基于结构的化学信息学的重要工具.
- 它预测蛋白质 - 连接体相互作用,结合亲和力,并通过虚拟选识别活性化合物.
- 现有的指标往往忽视了连接体的灵活性,影响了对接的准确性.
研究的目的:
- 引入新型联体B因子指数 (LBI),用于对接中优先考虑蛋白-联体复合体.
- 使用CASF-2016数据集评估LBI在提高对接性能方面的有效性.
- 评估LBI与实验性结合亲和力和重制成功的相关性.
主要方法:
- 定义LBI为结合部位和连接体之间的中位原子B因子的比.
- 使用评分函数比较评估 (CASF-2016) 数据集进行评估.
- 将LBI的业绩与其他指标和对接评分函数进行比较.
主要成果:
- 在实验中,LBI与实验性结合亲缘关系显示出中度的相关性 (斯皮尔曼 ρ ~ 0.48).
- 在预测绑定方面,LBI的表现优于几个标准的对接得分函数.
- 该指标与改进的重制成功相关 (RMSD < 2 Å),突出了其联体中心值.
结论:
- LBI是一种新的,可解释的,易于计算的指标,用于对接中优先考虑蛋白质 - 连接体复合体.
- 它在蛋白质B因子和分辨率指标上具有优势,尽管它的虚拟查实用程序需要进一步研究.
- LBI是免费的,以促进其在基于结构的化学信息学中的应用.
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