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Recent years have seen tremendous success in the design of novel drug molecules through deep generative models. Nevertheless, existing methods only generate drug-like molecules, which require additional structural optimization to be developed into actual drugs. In this study, a deep learning method for generating target-specific ligands was proposed. This method is useful when the dataset for target-specific ligands is limited. Deep learning methods can extract and learn features (representations) in a data-driven way with little or no human participation. Generative pretraining (GPT) was used to extract the contextual features of the molecule. Three different protein-encoding methods were used to extract the physicochemical properties and amino acid information of the target protein. Protein-encoding and molecular sequence information are combined to guide molecule generation. Transfer learning was used to fine-tune the pretrained model to generate molecules with better binding ability to the target protein. The model was validated using three different targets. The docking results show that our model is capable of generating new molecules with higher docking scores for the target proteins. [ABSTRACT FROM AUTHOR]

Background: Protein-protein interaction (PPI) is very important for many biochemical processes. Therefore, accurate prediction of PPI can help us better understand the role of proteins in biochemical processes. Although there are many methods to predict PPI in biology, they are time-consuming and lack accuracy, so it is necessary to build an efficiently and accurately computational model in the field of PPI prediction. Results: We present a novel sequence-based computational approach called DCSE (Double-Channel-Siamese-Ensemble) to predict potential PPI. In the encoding layer, we treat each amino acid as a word, and map it into an N-dimensional vector. In the feature extraction layer, we extract features from local and global perspectives by Multilayer Convolutional Neural Network (MCN) and Multilayer Bidirectional Gated Recurrent Unit with Convolutional Neural Networks (MBC). Finally, the output of the feature extraction layer is then fed into the prediction layer to output whether the input protein pair will interact each other. The MCN and MBC are siamese and ensemble based network, which can effectively improve the performance of the model. In order to demonstrate our model's performance, we compare it with four machine learning based and three deep learning based models. The results show that our method outperforms other models in all evaluation criteria. The Accuracy, Precision, F 1 , Recall and MCC of our model are 0.9303, 0.9091, 0.9268, 0.9452, 0.8609. For the other seven models, the highest Accuracy, Precision, F 1 , Recall and MCC are 0.9288, 0.9243, 0.9246, 0.9250, 0.8572. We also test our model in the imbalanced dataset and transfer our model to another species. The results show our model is excellent. Conclusion: Our model achieves the best performance by comparing it with seven other models. NLP-based coding method has a good effect on PPI prediction task. MCN and MBC extract protein sequence features from local and global perspectives and these two feature extraction layers are based on siamese and ensemble network structures. Siamese-based network structure can keep the features consistent and ensemble based network structure can effectively improve the accuracy of the model. [ABSTRACT FROM AUTHOR]

Machine learning (ML), especially deep learning (DL) techniques have been increasingly used in anomaly-based network intrusion detection systems (NIDS). However, ML/DL has shown to be extremely vulnerable to adversarial attacks, especially in such security-sensitive systems. Many adversarial attacks have been proposed to evaluate the robustness of ML-based NIDSs. Unfortunately, existing attacks mostly focused on feature-space and/or white-box attacks, which make impractical assumptions in real-world scenarios, leaving the study on practical gray/black-box attacks largely unexplored. To bridge this gap, we conduct the first systematic study of the gray/black-box traffic-space adversarial attacks to evaluate the robustness of ML-based NIDSs. Our work outperforms previous ones in the following aspects: (i) practical —the proposed attack can automatically mutate original traffic with extremely limited knowledge and affordable overhead while preserving its functionality; (ii) generic —the proposed attack is effective for evaluating the robustness of various NIDSs using diverse ML/DL models and non-payload-based features; (iii) explainable —we propose an explanation method for the fragile robustness of ML-based NIDSs. Based on this, we also propose a defense scheme against adversarial attacks to improve system robustness. We extensively evaluate the robustness of various NIDSs using diverse feature sets and ML/DL models. Experimental results show our attack is effective (e.g., >97% evasion rate in half cases for Kitsune, a state-of-the-art NIDS) with affordable execution cost and the proposed defense method can effectively mitigate such attacks (evasion rate is reduced by >50% in most cases). [ABSTRACT FROM AUTHOR]