AI-DPAPT:预测 PROTAC 活动的机器学习框架。

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-10-19 DOI:10.1007/s11030-024-11011-7
Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab
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引用次数: 0

摘要

蛋白质分解靶向嵌合体是靶向蛋白质降解(TPD)技术的一部分,对药理和治疗开发具有重要意义。小分子与靶向蛋白质的相互作用是一项复杂的工作,也是准确预测蛋白质的一项挑战。本研究利用机器学习算法和分子指纹技术建立了一个人工智能驱动的PROTAC活性预测工具,该工具可通过研究化学结构预测PROTAC活性。我们选择了一系列不同的 PROTAC 药物的化学结构及其相应的活性作为训练工具的数据集。本研究采用的流程包括数据准备、特征提取和模型训练。此外,还对 AdaBoost、支持向量机、随机森林、梯度提升和多层感知器等各种分类器的性能进行了评估。研究结果表明,这里所选的方法准确地描述了 PROTAC 活动。本研究中的所有模型的 ROC 曲线都优于 0.9,而随机森林在 AI-DPAPT 测试集上的曲线下面积得分为 0.97,从而显示出准确的结果。此外,该研究还揭示了可能影响 PROTAC 功能的分子特征。这些发现有可能加深人们对 TPD 所涉及的结构-活性相关性的理解。总之,这项研究通过引入这个由人工智能驱动的平台来预测 PROTAC 的功能,为计算药物开发做出了贡献。此外,它还加快了识别和改进以前未知药物的进程。AI-DPAPT 平台可通过网络服务器在线访问,网址是 https://ai-protac.streamlit.app/ 。
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AI-DPAPT: a machine learning framework for predicting PROTAC activity.

Proteolysis Targeting Chimeras are part of targeted protein degradation (TPD) techniques, which are significant for pharmacological and therapy development. Small-molecule interaction with the targeted protein is a complicated endeavor and a challenge to predict the proteins accurately. This study used machine learning algorithms and molecular fingerprinting techniques to build an AI-powered PROTAC Activity Prediction Tool that could predict PROTAC activity by examining chemical structures. The chemical structures of a diverse set of PROTAC drugs and their corresponding activities are selected as a dataset for training the tool. The processes used in this study included data preparation, feature extraction, and model training. Further, evaluation was done for the performance of the various classifiers, such as AdaBoost, Support Vector Machine, Random Forest, Gradient Boosting, and Multi-Layer Perceptron. The findings show that the methods selected here depict accurate PROTAC activities. All the models in this study showed an ROC curve better than 0.9, while the random forest on the test set of the AI-DPAPT had an area under the curve score of 0.97, thus showing accurate results. Furthermore, the study revealed significant insights into the molecular features that can influence the functions of the PROTAC. These findings can potentially increase the understanding of the structure-activity correlations involved in the TPD. Overall, the investigation contributes to computational drug development by introducing this platform powered by artificial intelligence that predicts the function of PROTAC. In addition, it sped up the processes of identifying and improving previously unknown medications. The AI-DPAPT platform can be accessed online using a web server at https://ai-protac.streamlit.app/ .

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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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