Interaction Prediction on BACE-1 Inhibitors Data for Alzheimer Disease using Message Passing Neural Network

Year 2025, Volume: 4 Issue: 1, 72 - 84, 18.02.2025

Suat Toraman , Bihter Daş

https://doi.org/10.62520/fujece.1466902

Abstract

The medical condition that develops as memory loss, dementia, and a general decrease in cognitive functions due to the death of brain cells over time is called Alzheimer's disease. This disease can lead to a gradual decline in cognitive functions and eventually severe memory losses that affect a person's daily life. Although the exact mechanism that causes Alzheimer's disease is not fully understood, it has been associated with certain structural changes in the brain, such as plaques and neurofibrillary bundles. This study investigates the use of geometric deep learning methods for the discovery of BACE-1 inhibitors that are promising in addressing Alzheimer's disease. Our study builds on these advancements by integrating GDL with pharmacological criteria, such as the QED criterion and Lipinski's rule, to predict BACE-1 inhibitors with enhanced accuracy and drug-like properties. Our model, which combines message-passing neural networks (MPNNs) and fully connected network (FCN) architectures, achieved a success rate of 87.7%. This performance not only surpasses that of previous studies but also ensures the practical applicability of our findings in drug discovery for Alzheimer's disease. The dual focus on prediction accuracy and drug likeness sets our work apart, providing a more comprehensive approach to identifying effective therapeutic agents.

Keywords

BACE-1 drug interaction, Alzheimer, Geometric deep learning, Graph network, BACE-1 inhibitors.

Ethical Statement

There is no need for an ethics committee approval in the prepared paper. There is no conflict of interest with any person/institution in the prepared paper.

Supporting Institution

TUBITAK

Project Number

123E098

Mesaj Aktarma Sinir Ağını Kullanarak Alzheimer Hastalığı için BACE-1 İnhibitörleri Verilerine İlişkin Etkileşim Tahmini

Abstract

Beyin hücrelerinin zamanla ölmesine bağlı olarak hafıza kaybı, demans ve bilişsel işlevlerde genel bir azalma şeklinde gelişen tıbbi duruma Alzheimer hastalığı denir. Bu hastalık, bilişsel işlevlerde kademeli bir düşüşe ve sonuçta kişinin günlük yaşamını etkileyen ciddi hafıza kayıplarına yol açabilmektedir. Alzheimer hastalığına neden olan mekanizma tam olarak anlaşılmamasına rağmen beyindeki plaklar ve nörofibriler demetler gibi bazı yapısal değişikliklerle ilişkilendirilmiştir. Bu çalışma, Alzheimer hastalığının tedavisinde ümit verici olan BACE-1 inhibitörlerinin keşfi için geometrik derin öğrenme yönteminin kullanımını araştırmaktadır. Eğitim sürecinde İletişim Geçiş Sinir Ağı ve Tamamen Bağlantılı Ağ kullanılarak özelleştirilmiş bir model geliştirilmiştir. Bu model, moleküler yapıların karmaşık özelliklerini yakalamak için grafik yerleştirmelerin ve tamamen bağlantılı ağların birleşimi yoluyla molekül etkileşimlerini tahmin etmektedir. Sonuçlar, geliştirilen modelin BACE-1 inhibitörlerinin etkileşimlerini başarılı bir şekilde tahmin edebildiğini göstermektedir. Modelin performans oranı %87,7 olarak belirlenmiştir. Bu çalışma, Alzheimer hastalığına yönelik yeni BACE-1 inhibitörlerinin keşfedilmesi ve geliştirilmesi için umut verici bir yol haritası sunmaktadır.

Keywords

BACE-1 ilaç etkileşimi, Alzheimer hastalığı, Geometrik derin öğrenme, Grafik ağı, BACE-1 inhibitörleri

Project Number

123E098

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