The drug repurposing of known approved drugs (e.g., lopinavir/ritonavir) has failed to treat SARS-CoV-2-infected patients. Therefore, it is important to generate new chemical entities against this virus. As a critical enzyme in the lifecycle of the coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive target for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with a fragment-based drug design (ADQN–FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from the lead compounds based on our structure-based optimization policy (SBOP). All of the 47 lead compounds obtained directly with our AI model and related derivatives based on the SBOP are accessible in our molecular library. These compounds can be used as potential candidates by researchers to develop drugs against SARS-CoV-2.

RNA modification plays an indispensable role in the regulation of organisms. RNA modification site prediction offers an insight into diverse cellular processing. Regarding different types of RNA modification site prediction, it is difficult to tell the most relevant feature combinations from a variant of RNA properties. Thereby, the performance of traditional machine learning based predictors relied on the skill of feature engineering. As a data-driven approach, deep learning can detect optimal feature patterns to represent input data. In this study, we developed a predictor for multiple types of RNA modifications method called DeepMRMP (Multiple Types RNA Modification Sites Predictor), which is based on the bidirectional Gated Recurrent Unit (BGRU) and transfer learning. DeepMRMP makes full use of multiple RNA site modification data and correlation among them to build predictor for different types of RNA modification sites. Through 10-fold cross-validation of the RNA sequences of H. sapiens, M. musculus and S. cerevisiae, DeepMRMP acted as a reliable computational tool for identifying N¹-methyladenosine (m¹A), pseudouridine (Ψ), 5-methylcytosine (m⁵C) modification sites.

Membrane proteins (MPs) are involved in many essential biomolecule mechanisms as a pivotal factor in enabling the small molecule and signal transport between the two sides of the biological membrane; this is the reason that a large portion of modern medicinal drugs target MPs. Therefore, accurately identifying the membrane protein-ligand binding sites (MPLs) will significantly improve drug discovery. In this paper, we propose a sequence-based MPLs predictor called MPLs-Pred, where evolutionary profiles, topology structure, physicochemical properties, and primary sequence segment descriptors are combined as features applied to a random forest classifier, and an under-sampling scheme is used to enhance the classification capability with imbalanced samples. Additional ligand-specific models were taken into consideration in refining the prediction. The corresponding experimental results based on our method achieved an appreciable performance, with 0.63 MCC (Matthews correlation coefficient) as the overall prediction precision, and those values were 0.604, 0.7, and 0.692, respectively, for the three main types of ligands: drugs, metal ions, and biomacromolecules. MPLs-Pred is freely accessible at http://icdtools.nenu.edu.cn/.

Clustering analysis, as an important technique in data mining, aims to identify the nature groups or clusters of data objects in the attribute space. Data objects in real-world applications are commonly described by both numeric and categorical attributes. In this research, considering that the partitional clustering algorithms designed for this type of mixed data are prone to get trapped into local optima and the cuckoo search approach is efficient in solving global optimization problems, we propose CCS-K-Prototypes, a novel partitional Clustering algorithm based on Cuckoo Search and K-Prototypes, for clustering mixed numeric and categorical data. To deal with different types of attributes, we develop a novel representation for candidate solutions, and suggest two formulas for the cuckoo to search for the potential solution around the existing solutions or in the entire attribute space. Finally, the performance of the proposed algorithm is assessed by a series of experiments on five benchmark datasets.

Clustering data with both numeric and categorical attributes is of great importance as such data are ubiquitous in real-world problems. Multi-view learning approaches have proven to be more effective and having better generalisation ability compared to single-view learning in many problems. However, most of the existing clustering algorithms developed for mixed numeric and categorical data are single-view. In this research, we propose a novel multi-view clustering algorithm based on the k-prototypes (which we term Multi-view K-Prototypes) for clustering mixed data. To the best of our knowledge, our proposed Multi-view K-Prototypes is the first multi-view version of the well-known k-prototypes algorithm. To cluster the mixed data over multiple views, we present a novel representation prototype of cluster centres in the scenario of multiple views, and we also devise formulas for updating the cluster centres over each view. Then we propose the concept of consensus cluster centres to output the final clustering result. Finally, we carried out a series of experiments on four benchmark datasets to assess the performance of the proposed Multi-view K-Prototypes clustering. Experimental results show that the Multi-view K-Prototypes algorithm outperforms the seven state-of-the-art algorithms in most cases.

Post-translational modifications (PTMs) regulate protein function, stability, and interactions, playing essential roles in cellular signaling, localization, and disease mechanisms. Computational approaches enable scalable PTM site prediction; however, traditional models focus only on local sequence features from fragments around potential modification sites, limiting the scope of their predictions. Recently, pre-trained protein language models (PLMs) have improved PTM prediction by leveraging biological knowledge derived from extensive protein databases. However, most PLMs used for PTM site prediction are pre-trained solely on amino acid sequences, limiting their ability to capture the structural context necessary for accurate PTM site prediction. Moreover, these methods typically train separate single-task models for each PTM type, which hinders the sharing of common features and limits potential knowledge transfer across tasks. To overcome these limitations, we introduce MTPrompt-PTM, a multi-task PTM prediction framework developed by applying prompt tuning to a structure-aware protein language model (S-PLM). Instead of training several single-task models, MTPrompt-PTM trains one multi-task model to predict multiple types of PTM sites using shared feature extraction layers and task-specific classification heads. Additionally, we incorporate a knowledge distillation strategy to enhance the efficiency and generalizability of multi-task training. Experimental results demonstrate that MTPrompt-PTM outperforms state-of-the-art PTM prediction tools on 13 types of PTM sites, highlighting the advantages of multi-task learning and structural integration.