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Ligands

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Comprehensive Exploration of Target-specific Ligands Using a Graph Convolution Neural Network.

Molecular informatics
Machine learning approaches are widely used to evaluate ligand activities of chemical compounds toward potential target proteins. Especially, exploration of highly selective ligands is important for the development of new drugs with higher safety. On...

Integrated structural modeling and super-resolution imaging resolve GPCR oligomers.

Progress in molecular biology and translational science
Formation of G protein-coupled receptors (GPCRs) dimers and higher order oligomers represents a key mechanism in pleiotropic signaling, yet how individual protomers function within oligomers remains poorly understood. For the Class A/rhodopsin subfam...

Development of New Methods Needs Proper Evaluation-Benchmarking Sets for Machine Learning Experiments for Class A GPCRs.

Journal of chemical information and modeling
New computational approaches for virtual screening applications are constantly being developed. However, before a particular tool is used to search for new active compounds, its effectiveness in the type of task must be examined. In this study, we co...

MathDL: mathematical deep learning for D3R Grand Challenge 4.

Journal of computer-aided molecular design
We present the performances of our mathematical deep learning (MathDL) models for D3R Grand Challenge 4 (GC4). This challenge involves pose prediction, affinity ranking, and free energy estimation for beta secretase 1 (BACE) as well as affinity ranki...

Exploring fragment-based target-specific ranking protocol with machine learning on cathepsin S.

Journal of computer-aided molecular design
Cathepsin S (CatS), a member of cysteine cathepsin proteases, has been well studied due to its significant role in many pathological processes, including arthritis, cancer and cardiovascular diseases. CatS inhibitors have been included in D3R-GC3 for...

Nonparametric chemical descriptors for the calculation of ligand-biopolymer affinities with machine-learning scoring functions.

Journal of computer-aided molecular design
The computational prediction of ligand-biopolymer affinities is a crucial endeavor in modern drug discovery and one that still poses major challenges. The choice of the appropriate computational method often reveals itself as a trade-off between accu...

Incorporating Explicit Water Molecules and Ligand Conformation Stability in Machine-Learning Scoring Functions.

Journal of chemical information and modeling
Structure-based drug design is critically dependent on accuracy of molecular docking scoring functions, and there is of significant interest to advance scoring functions with machine learning approaches. In this work, by judiciously expanding the tra...

Recognizing five molecular ligand-binding sites with similar chemical structure.

Journal of computational chemistry
Accurate identification of ligand-binding sites and discovering the protein-ligand interaction mechanism are important for understanding proteins' functions and designing new drugs. Meanwhile, accurate computational prediction and mechanism research ...

Computational methods and tools for binding site recognition between proteins and small molecules: from classical geometrical approaches to modern machine learning strategies.

Journal of computer-aided molecular design
In the current "genomic era" the number of identified genes is growing exponentially. However, the biological function of a large number of the corresponding proteins is still unknown. Recognition of small molecule ligands (e.g., substrates, inhibito...

Graph Convolutional Neural Networks for Predicting Drug-Target Interactions.

Journal of chemical information and modeling
Accurate determination of target-ligand interactions is crucial in the drug discovery process. In this paper, we propose a graph-convolutional (Graph-CNN) framework for predicting protein-ligand interactions. First, we built an unsupervised graph-aut...