AI-DPAPT: a machine learning framework for predicting PROTAC activity.

Mol Divers

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, 22516, El-Buhaira, Egypt.

Published: October 2024

AI Article Synopsis

  • Proteolysis Targeting Chimeras (PROTACs) are innovative tools in targeted protein degradation (TPD) that hold promise for drug development, but predicting their effectiveness is challenging.
  • This study introduces an AI-powered PROTAC Activity Prediction Tool (AI-DPAPT) that leverages machine learning and molecular fingerprinting techniques to accurately predict PROTAC activity based on chemical structures.
  • The research demonstrated strong performance across various machine learning classifiers, with the Random Forest model yielding an impressive area under the curve score of 0.97, enhancing the understanding of structure-activity relationships in TPD and potentially accelerating drug development processes.

Article Abstract

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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Source
http://dx.doi.org/10.1007/s11030-024-11011-7DOI Listing

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