NAD_MCNN: Combining Protein Language Models and Multiwindow Convolutional Neural Networks for Deacetylase NAD+ Binding Site Prediction.

Journal: Chemical biology & drug design
PMID:

Abstract

Sirtuins, a class of NAD+ -dependent deacetylases, play a key role in aging, metabolism, and longevity. Their interaction with NAD+ at the catalytic site is crucial for function, but experimental methods to map NAD+ binding sites are time consuming. To address this, we developed a computational method integrating pretrained protein language models with multiwindow convolutional neural networks (CNNs). This method captures sequence information and diverse local patterns, achieving state-of-the-art performance, with AUC of 0.9733 for human sirtuin proteins and 0.9701 for other NAD-dependent deacylation enzymes. These findings offer insights into the role of sirtuins in aging and their broader biological functions while providing a new path for identifying therapeutic targets in aging-related diseases.

Authors

  • Van-The Le
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, 32003, Taiwan.
  • Yu-Chen Liu
    Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Yan-Yun Chang
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li 32003, Taiwan.
  • Yu-Cheng Lee
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, 32003, Taiwan.
  • Yi-Jing Lin
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li 32003, Taiwan.
  • Muhammad-Shahid Malik
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, 32003, Taiwan; Department of Computer Science and Engineering, Karakoram International University, Pakistan.
  • Yu-Yen Ou
    Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, 32003, Taiwan. Electronic address: yien@saturn.yzu.edu.tw.