Target-specific drug design method combining deep learning and water pharmacophore

Author(s):  
Cho Art
Author(s):  
Minsup Kim ◽  
Kichul Park ◽  
Wonsang Kim ◽  
Sangwon Jung ◽  
Art E. Cho

2019 ◽  
Author(s):  
Mohammad Rezaei ◽  
Yanjun Li ◽  
Xiaolin Li ◽  
Chenglong Li

<b>Introduction:</b> The ability to discriminate among ligands binding to the same protein target in terms of their relative binding affinity lies at the heart of structure-based drug design. Any improvement in the accuracy and reliability of binding affinity prediction methods decreases the discrepancy between experimental and computational results.<br><b>Objectives:</b> The primary objectives were to find the most relevant features affecting binding affinity prediction, least use of manual feature engineering, and improving the reliability of binding affinity prediction using efficient deep learning models by tuning the model hyperparameters.<br><b>Methods:</b> The binding site of target proteins was represented as a grid box around their bound ligand. Both binary and distance-dependent occupancies were examined for how an atom affects its neighbor voxels in this grid. A combination of different features including ANOLEA, ligand elements, and Arpeggio atom types were used to represent the input. An efficient convolutional neural network (CNN) architecture, DeepAtom, was developed, trained and tested on the PDBbind v2016 dataset. Additionally an extended benchmark dataset was compiled to train and evaluate the models.<br><b>Results: </b>The best DeepAtom model showed an improved accuracy in the binding affinity prediction on PDBbind core subset (Pearson’s R=0.83) and is better than the recent state-of-the-art models in this field. In addition when the DeepAtom model was trained on our proposed benchmark dataset, it yields higher correlation compared to the baseline which confirms the value of our model.<br><b>Conclusions:</b> The promising results for the predicted binding affinities is expected to pave the way for embedding deep learning models in virtual screening and rational drug design fields.


2021 ◽  
Vol 61 (2) ◽  
pp. 621-630
Author(s):  
Sowmya Ramaswamy Krishnan ◽  
Navneet Bung ◽  
Gopalakrishnan Bulusu ◽  
Arijit Roy

IEEE Access ◽  
2021 ◽  
pp. 1-1
Author(s):  
Aimin Zhou ◽  
Hongbin Liu ◽  
Shutao Zhang ◽  
Jinyan Ouyang

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Surayya Ado Bala ◽  
Shri Ojha Kant ◽  
Adamu Garba Yakasai

Over the last decade, deep learning (DL) methods have been extremely successful and widely used in almost every domain. Researchers are now focusing on the convergence of medical imaging and drug design using deep learning to revolutionize medical diagnostic and improvement in the monitoring from response to therapy. DL a new machine learning paradigm that focuses on learning with deep hierarchical models of data. Medical imaging has transformed healthcare science, it was thought of as a diagnostic tool for disease, but now it is also used in drug design. Advances in medical imaging technology have enabled scientists to detect events at the cellular level. The role of medical imaging in drug design includes identification of likely responders, detection, diagnosis, evaluation, therapy monitoring, and follow-up. A qualitative medical image is transformed into a quantitative biomarker or surrogate endpoint useful in drug design decision-making. For this, a parameter needs to be identified that characterizes the disease baseline and its subsequent response to treatment. The result is a quantifiable improvement in healthcare quality in most therapeutic areas, resulting in improvements in quality and duration of life. This paper provides an overview of recent studies on applying the deep learning method in medical imaging and drug design. We briefly discuss the fields related to the history of deep learning, medical imaging, and drug design.


2017 ◽  
Vol 398 (12) ◽  
pp. 1319-1325 ◽  
Author(s):  
Yang Chen ◽  
Yu Cao

AbstractSphingomyelin (SM) is among the most important biomolecules in eukaryotes and acts as both constructive components and signal carrier in physiological processes. SM is catalyzed by a membrane protein family, sphingomyelin synthases (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate sphingomyelin and other sphingolipids levels, thereby regulating membrane mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathways. SMSs was found associated with various diseases. Downregulation of SMS2 activity results in protective effects against obesity, atherosclerosis and diabetes and makes SMS2 inhibitors potential medicines. Structural guided specific drug design could be the next breakthrough, discriminating SMS2 from other homologs.


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