Functional peptides play crucial roles in various biological processes and hold significant potential in many fields such as drug discovery and biotechnology. Accurately predicting the functions of peptides is essential for understanding their diverse effects and designing peptide-based therapeutics. Here, we propose CELA-MFP, a deep learning framework that incorporates feature Contrastive Enhancement and Label Adaptation for predicting Multi-Functional therapeutic Peptides. CELA-MFP utilizes a protein language model (pLM) to extract features from peptide sequences, which are then fed into a Transformer decoder for function prediction, effectively modeling correlations between different functions. To enhance the representation of each peptide sequence, contrastive learning is employed during training. Experimental results demonstrate that CELA-MFP outperforms state-of-the-art methods on most evaluation metrics for two widely used datasets, MFBP and MFTP. The interpretability of CELA-MFP is demonstrated by visualizing attention patterns in pLM and Transformer decoder. Finally, a user-friendly online server for predicting multi-functional peptides is established as the implementation of the proposed CELA-MFP and can be freely accessed at http://dreamai.cmii.online/CELA-MFP.

Recently, peptide-based drugs have gained unprecedented interest in discovering and developing antifungal drugs due to their high efficacy, broad-spectrum activity, low toxicity and few side effects. However, it is time-consuming and expensive to identify antifungal peptides (AFPs) experimentally. Therefore, computational methods for accurately predicting AFPs are highly required. In this work, we develop AFP-MFL, a novel deep learning model that predicts AFPs only relying on peptide sequences without using any structural information. AFP-MFL first constructs comprehensive feature profiles of AFPs, including contextual semantic information derived from a pre-trained protein language model, evolutionary information, and physicochemical properties. Subsequently, the co-attention mechanism is utilized to integrate contextual semantic information with evolutionary information and physicochemical properties separately. Extensive experiments show that AFP-MFL outperforms state-of-the-art models on four independent test datasets. Furthermore, the SHAP method is employed to explore each feature contribution to the AFPs prediction. Finally, a user-friendly web server of the proposed AFP-MFL is developed and freely accessible at http://inner.wei-group.net/AFPMFL/, which can be considered as a powerful tool for the rapid screening and identification of novel AFPs.

MOTIVATION: Identifying the functional sites of a protein, such as the binding sites of proteins, peptides, or other biological components, is crucial for understanding related biological processes and drug design. However, existing sequence-based methods have limited predictive accuracy, as they only consider sequence-adjacent contextual features and lack structural information. RESULTS: In this study, DeepProSite is presented as a new framework for identifying protein binding site that utilizes protein structure and sequence information. DeepProSite first generates protein structures from ESMFold and sequence representations from pretrained language models. It then uses Graph Transformer and formulates binding site predictions as graph node classifications. In predicting protein-protein/peptide binding sites, DeepProSite outperforms state-of-the-art sequence- and structure-based methods on most metrics. Moreover, DeepProSite maintains its performance when predicting unbound structures, in contrast to competing structure-based prediction methods. DeepProSite is also extended to the prediction of binding sites for nucleic acids and other ligands, verifying its generalization capability. Finally, an online server for predicting multiple types of residue is established as the implementation of the proposed DeepProSite. AVAILABILITY AND IMPLEMENTATION: The datasets and source codes can be accessed at https://github.com/WeiLab-Biology/DeepProSite. The proposed DeepProSite can be accessed at https://inner.wei-group.net/DeepProSite/.

One of the main problems with the joint use of multiple drugs is that it may cause adverse drug interactions and side effects that damage the body. Therefore, it is important to predict potential drug interactions. However, most of the available prediction methods can only predict whether two drugs interact or not, whereas few methods can predict interaction events between two drugs. Accurately predicting interaction events of two drugs is more useful for researchers to study the mechanism of the interaction of two drugs. In the present study, we propose a novel method, MDF-SA-DDI, which predicts drug-drug interaction (DDI) events based on multi-source drug fusion, multi-source feature fusion and transformer self-attention mechanism. MDF-SA-DDI is mainly composed of two parts: multi-source drug fusion and multi-source feature fusion. First, we combine two drugs in four different ways and input the combined drug feature representation into four different drug fusion networks (Siamese network, convolutional neural network and two auto-encoders) to obtain the latent feature vectors of the drug pairs, in which the two auto-encoders have the same structure, and their main difference is the number of neurons in the input layer of the two auto-encoders. Then, we use transformer blocks that include self-attention mechanism to perform latent feature fusion. We conducted experiments on three different tasks with two datasets. On the small dataset, the area under the precision-recall-curve (AUPR) and F1 scores of our method on task 1 reached 0.9737 and 0.8878, respectively, which were better than the state-of-the-art method. On the large dataset, the AUPR and F1 scores of our method on task 1 reached 0.9773 and 0.9117, respectively. In task 2 and task 3 of two datasets, our method also achieved the same or better performance as the state-of-the-art method. More importantly, the case studies on five DDI events are conducted and achieved satisfactory performance. The source codes and data are available at https://github.com/ShenggengLin/MDF-SA-DDI.