相关实验视频

Updated: Jun 14, 2025

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

利用多种数据类型来改善化合物酶生物活性预测

Ryan Theisen¹, Tianduanyi Wang², Balaguru Ravikumar²

¹Harmonic Discovery Inc., New York City, NY, USA. rayees@harmonicdiscovery.com.

Nature communications

|August 31, 2024

概括

本研究引入了一种机器学习方法,用于使用单剂量和剂量反应数据预测化合物激酶活性. 新方法提高了预测准确性,提高了数据集开发效率.

科学领域:

计算化学和化学信息学
药物的发现和开发.
机器学习在药理学中的应用.

背景情况:

机器学习 (ML) 模型对于预测化合物-酶相互作用至关重要.
现有的ML模型往往忽略了单剂量生物活性数据中的有价值信息,仅依赖剂量反应数据.
这种局限性阻碍了可用的实验结果的全面利用.

研究的目的:

开发和验证一种新的ML方法来预测化合物酶活性,该方法集成了单剂量和剂量反应生物活性数据.
为了提高预测化合物-激酶相互作用的准确性和效率.
提高用于预测模型的培训数据集的成本效益.

主要方法:

开发了一种两阶段的机器学习方法,以利用各种生物活性数据类型.
该方法在五种不同的机器学习算法中进行了评估.
实验验证对347个选择的化合物-激酶对进行了实验验证,使用了表现最佳的模型.

主要成果:

拟议的两阶段方法显著改善了模型性能,而不是仅仅在剂量反应数据上训练的模型.
在实验分析中,表现最好的模型实现了40%的命中率和78%的负预测值.
纳入模型不确定性估计进一步提高了复合物选择中的预测率.

结论:

整合多种生物活性数据类型,包括单剂量测量,可以更准确地预测化合物酶活性.
开发的ML方法提供了一个更有效和更具成本效益的策略来构建培训数据集.
这种方法在加速药物发现和开发管道方面具有重大前景.

更多相关视频

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

相关概念视频

Protein Networks

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...