Identification of Potential Parkinson’s Disease Drugs Based on Multi-Source Data Fusion and Convolutional Neural Network

Abstract

Parkinson’s disease (PD) is a serious neurodegenerative disease. Most of the current treatment can only alleviate symptoms, but not stop the progress of the disease. Therefore, it is crucial to find medicines to completely cure PD. Finding new indications of existing drugs through drug repositioning can not only reduce risk and cost, but also improve research and development efficiently. A drug repurposing method was proposed to identify potential Parkinson’s disease-related drugs based on multi-source data integration and convolutional neural network. Multi-source data were used to construct similarity networks, and topology information were utilized to characterize drugs and PD-associated proteins. Then, diffusion component analysis method was employed to reduce the feature dimension. Finally, a convolutional neural network model was constructed to identify potential associations between existing drugs and LProts (PD-associated proteins). Based on 10-fold cross-validation, the developed method achieved an accuracy of 91.57%, specificity of 87.24%, sensitivity of 95.27%, Matthews correlation coefficient of 0.8304, area under the receiver operating characteristic curve of 0.9731 and area under the precision–recall curve of 0.9727, respectively. Compared with the state-of-the-art approaches, the current method demonstrates superiority in some aspects, such as sensitivity, accuracy, robustness, etc. In addition, some of the predicted potential PD therapeutics through molecular docking further proved that they can exert their efficacy by acting on the known targets of PD, and may be potential PD therapeutic drugs for further experimental research. It is anticipated that the current method may be considered as a powerful tool for drug repurposing and pathological mechanism studies.

Computer-Aided Drug Design towards New Psychotropic and Neurological Drugs

“…The top 10 ranked compounds from the unknown samples underwent molecular docking against the 5-hydroxytryptamine receptor 2A (5HTR2A) to ascertain favourable interactions between these ligands and the target proteins. Pimvanserin was used as a positive control, for which three of the ten ligands had comparable binding energy, of which the topoisomerase inhibitor topotecan ( 4 , Figure 4 B) was the most promising [ 137 ].…”

Role of Computer-Aided Drug Design in Drug Development

“…Besides, Liu et al's work [15] provides an application example of drug repurposing using data-driven methods. Specifically, their work constructed a convolutional neural network model to search for potential ligands targeting Parkinson's disease-associated proteins (LProts) among existing drugs.…”