Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab
{"title":"AI-DPAPT:预测 PROTAC 活动的机器学习框架。","authors":"Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab","doi":"10.1007/s11030-024-11011-7","DOIUrl":null,"url":null,"abstract":"<p><p>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/ .</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"AI-DPAPT: a machine learning framework for predicting PROTAC activity.\",\"authors\":\"Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab\",\"doi\":\"10.1007/s11030-024-11011-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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/ .</p>\",\"PeriodicalId\":708,\"journal\":{\"name\":\"Molecular Diversity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Diversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11030-024-11011-7\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-11011-7","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
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/ .
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;