Background: The identification of DNA binding proteins (DBP) is an important research field. Experiment-based methods are time-consuming and labor-intensive for detecting DBP. Objective: To solve the problem of large-scale DBP identification, some machine learning methods are proposed. However, these methods have insufficient predictive accuracy. Our aim is to develop a sequence- based machine learning model to predict DBP. Methods: In our study, we extracted six types of features (including NMBAC, GE, MCD, PSSM-AB, PSSM-DWT, and PsePSSM) from protein sequences. We used Multiple Kernel Learning based on Hilbert- Schmidt Independence Criterion (MKL-HSIC) to estimate the optimal kernel. Then, we constructed a hypergraph model to describe the relationship between labeled and unlabeled samples. Finally, Laplacian Support Vector Machines (LapSVM) is employed to train the predictive model. Our method is tested on PDB186, PDB1075, PDB2272 and PDB14189 data sets. Result: Compared with other methods, our model achieved best results on benchmark data sets. Conclusion: The accuracy of 87.1% and 74.2% are achieved on PDB186 (Independent test of PDB1075) and PDB2272 (Independent test of PDB14189), respectively.

Background: RNA secondary structure prediction is an important issue in structural bioinformatics, and RNA pseudoknotted secondary structure prediction represents an NP-hard problem. Recently, many different machine-learning methods, Markov models, and neural networks have been employed for this problem, with encouraging results regarding their predictive accuracy; however, their performances are usually limited by the requirements of the learning model and over-fitting, which requires use of a fixed number of training features. Because most natural biological sequences have variable lengths, the sequences have to be truncated before the features are employed by the learning model, which not only leads to the loss of information but also destroys biological-sequence integrity. Results: To address this problem, we propose an adaptive sequence length based on deep-learning model and integrate an energy-based filter to remove the over-fitting base pairs. Conclusions: Comparative experiments conducted on an authoritative dataset RNA STRAND (RNA secondary STRucture and statistical Analysis Database) revealed a 12% higher accuracy relative to three currently used methods.

Biologically important effects occur when proteins bind to other substances, of which binding to DNA is a crucial one. Therefore, accurate identification of protein-DNA binding residues is important for further understanding of the protein-DNA interaction mechanism. Although wet-lab methods can accurately obtain the location of bound residues, it requires significant human, financial and time costs. There is thus an urgent need to develop efficient computational-based methods. Most current state-of-the-art methods are two-step approaches: the first step uses a sliding window technique to extract residue features; the second step uses each residue as an input to the model for prediction. This has a negative impact on the efficiency of prediction and ease of use. In this study, we propose a sequence-to-sequence (seq2seq) model that can input the entire protein sequence of variable length and use two modules, Transformer Encoder Block and Feature Extracting Block, for hierarchical feature extraction, where Transformer Encoder Block is used to extract global features, and then Feature Extracting Block is used to extract local features to further improve the recognition capability of the model. The comparison results on two benchmark datasets, namely PDNA-543 and PDNA-41, prove the effectiveness of our method in identifying protein-DNA binding residues. The code is available at https://github.com/ShixuanGG/DNA-protein_binding_residues.

This study aims to tackle the intricate challenge of predicting RNA-small molecule binding sites to explore the potential value in the field of RNA drug targets. To address this challenge, we propose the MultiModRLBP method, which integrates multi-modal features using deep learning algorithms. These features include 3D structural properties at the nucleotide base level of the RNA molecule, relational graphs based on overall RNA structure, and rich RNA semantic information. In our investigation, we gathered 851 interactions between RNA and small molecule ligand from the RNAglib dataset and RLBind training set. Unlike conventional training sets, this collection broadened its scope by including RNA complexes that have the same RNA sequence but change their respective binding sites due to structural differences or the presence of different ligands. This enhancement enables the MultiModRLBP model to more accurately capture subtle changes at the structural level, ultimately improving its ability to discern nuances among similar RNA conformations. Furthermore, we evaluated MultiModRLBP on two classic test sets, Test18 and Test3, highlighting its performance disparities on small molecules based on metal and non-metal ions. Additionally, we conducted a structural sensitivity analysis on specific complex categories, considering RNA instances with varying degrees of structural changes and whether they share the same ligands. The research results indicate that MultiModRLBP outperforms the current state-of-the-art methods on multiple classic test sets, particularly excelling in predicting binding sites for non-metal ions and instances where the binding sites are widely distributed along the sequence. MultiModRLBP also can be used as a potential tool when the RNA structure is perturbed or the RNA experimental tertiary structure is not available. Most importantly, MultiModRLBP exhibits the capability to distinguish binding characteristics of RNA that are structurally diverse yet exhibit sequence similarity. These advancements hold promise in reducing the costs associated with the development of RNA-targeted drugs.