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Updated: Jun 18, 2025

Large-Scale Screens of Metagenomic Libraries

Large-Scale Screens of Metagenomic Libraries

Published on: May 28, 2007

识别来自大型图书馆对接的文物

Yujin Wu¹, Fangyu Liu¹, Isabella Glenn¹

¹Department of Pharmaceutical Chemistry, University of California, San Francisco, 94158, United States.

bioRxiv : the preprint server for biology

|July 29, 2024

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此摘要是机器生成的。

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查看所有相关文章

计算药物发现面临着挑战,因为大型图书馆会产生错误的阳性结果. 使用直角方法恢复顶部对接点击可以有效地识别和删除这些文物,提高药物开发虚拟选的准确性.

科学领域:

计算化学的计算化学
药物发现药物发现药物发现
生物化学生化学

背景情况:

通过分子对接进行大规模的虚拟选是识别潜在药物候选者的强大工具.
在对接屏幕中增加图书馆大小可能会导致在排名第一的组合中,得分函数文物或"作弊者"的流行率更高.
这些文物可能很少见,但随着选图书馆的扩大,它们变得越来越占主导地位,可能会阻碍真实连接体的识别.

研究的目的:

为了研究从对接屏幕中恢复排名最高的分子的有效性,使用直角方法来识别和过出文物.
探索隐性溶剂模型和绝对结合的自由能量扰动 (AB-FEP) 作为交叉验证过器的实用性.
验证一种新的策略,以提高大规模虚拟查结果的可靠性.

主要方法:

在九个不同的生物标中对恢复方法的回顾性验证.
该方法的未来应用在一个大型图书馆对抗AmpCβ-lactamase的对接屏幕上.
通过对接和重组识别的优先化合物的合成和实验性酶抑制测定.

主要成果:

在回顾性研究中,直角复合法成功地降低了高级非结合物的优先级,同时保留了真正的连接体.
在前性AmpCβ-lactamase研究中,标记为工件的39种化合物中,没有一种抑制了酶.

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Last Updated: Jun 18, 2025

Large-Scale Screens of Metagenomic Libraries

Large-Scale Screens of Metagenomic Libraries

Published on: May 28, 2007

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

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Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities

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在89种被确定为可信的真正活性物质的化合物中,57%显示酶抑制,其中19种表现出强烈活性 (明显IC50<1μM).

结论:

使用直角方法恢复顶部对接的成功,例如隐性溶剂模型和AB-FEP,是识别和删除计算工件的有效策略.
这种方法显著提高了大型图书馆对接屏幕的击中质量,减少了假阳性.
拟议的方法有望在药物发现中得到广泛采用,因为选图书馆的数量继续增长.