De Novo Peptide and Protein Design Using Generative Adversarial Networks: An Update.

Lin E ，Lin CH ，Lane HY 《-》

Relevant Applications of Generative Adversarial Networks in Drug Design and Discovery: Molecular De Novo Design, Dimensionality Reduction, and De Novo Peptide and Protein Design.

Lin E ，Lin CH ，Lane HY 《MOLECULES》

Artificial intelligence to deep learning: machine intelligence approach for drug discovery.

Drug designing and development is an important area of research for pharmaceutical companies and chemical scientists. However, low efficacy, off-target delivery, time consumption, and high cost impose a hurdle and challenges that impact drug design and discovery. Further, complex and big data from genomics, proteomics, microarray data, and clinical trials also impose an obstacle in the drug discovery pipeline. Artificial intelligence and machine learning technology play a crucial role in drug discovery and development. In other words, artificial neural networks and deep learning algorithms have modernized the area. Machine learning and deep learning algorithms have been implemented in several drug discovery processes such as peptide synthesis, structure-based virtual screening, ligand-based virtual screening, toxicity prediction, drug monitoring and release, pharmacophore modeling, quantitative structure-activity relationship, drug repositioning, polypharmacology, and physiochemical activity. Evidence from the past strengthens the implementation of artificial intelligence and deep learning in this field. Moreover, novel data mining, curation, and management techniques provided critical support to recently developed modeling algorithms. In summary, artificial intelligence and deep learning advancements provide an excellent opportunity for rational drug design and discovery process, which will eventually impact mankind. The primary concern associated with drug design and development is time consumption and production cost. Further, inefficiency, inaccurate target delivery, and inappropriate dosage are other hurdles that inhibit the process of drug delivery and development. With advancements in technology, computer-aided drug design integrating artificial intelligence algorithms can eliminate the challenges and hurdles of traditional drug design and development. Artificial intelligence is referred to as superset comprising machine learning, whereas machine learning comprises supervised learning, unsupervised learning, and reinforcement learning. Further, deep learning, a subset of machine learning, has been extensively implemented in drug design and development. The artificial neural network, deep neural network, support vector machines, classification and regression, generative adversarial networks, symbolic learning, and meta-learning are examples of the algorithms applied to the drug design and discovery process. Artificial intelligence has been applied to different areas of drug design and development process, such as from peptide synthesis to molecule design, virtual screening to molecular docking, quantitative structure-activity relationship to drug repositioning, protein misfolding to protein-protein interactions, and molecular pathway identification to polypharmacology. Artificial intelligence principles have been applied to the classification of active and inactive, monitoring drug release, pre-clinical and clinical development, primary and secondary drug screening, biomarker development, pharmaceutical manufacturing, bioactivity identification and physiochemical properties, prediction of toxicity, and identification of mode of action.

Gupta R ，Srivastava D ，Sahu M ，Tiwari S ，Ambasta RK ，Kumar P ... -  《-》

Generative machine learning for de novo drug discovery: A systematic review.

Recent research on artificial intelligence indicates that machine learning algorithms can auto-generate novel drug-like molecules. Generative models have revolutionized de novo drug discovery, rendering the explorative process more efficient. Several model frameworks and input formats have been proposed to enhance the performance of intelligent algorithms in generative molecular design. In this systematic literature review of experimental articles and reviews over the last five years, machine learning models, challenges associated with computational molecule design along with proposed solutions, and molecular encoding methods are discussed. A query-based search of the PubMed, ScienceDirect, Springer, Wiley Online Library, arXiv, MDPI, bioRxiv, and IEEE Xplore databases yielded 87 studies. Twelve additional studies were identified via citation searching. Of the articles in which machine learning was implemented, six prominent algorithms were identified: long short-term memory recurrent neural networks (LSTM-RNNs), variational autoencoders (VAEs), generative adversarial networks (GANs), adversarial autoencoders (AAEs), evolutionary algorithms, and gated recurrent unit (GRU-RNNs). Furthermore, eight central challenges were designated: homogeneity of generated molecular libraries, deficient synthesizability, limited assay data, model interpretability, incapacity for multi-property optimization, incomparability, restricted molecule size, and uncertainty in model evaluation. Molecules were encoded either as strings, which were occasionally augmented using randomization, as 2D graphs, or as 3D graphs. Statistical analysis and visualization are performed to illustrate how approaches to machine learning in de novo drug design have evolved over the past five years. Finally, future opportunities and reservations are discussed.

Martinelli DD 《-》

Generative chemistry: drug discovery with deep learning generative models.

Bian Y ，Xie XQ 《-》