Accurate and rapid prediction of protein-ligand binding affinity is a great challenge currently encountered in drug discovery. Recent advances have manifested a promising alternative in applying deep learning-based computational approaches for accurately quantifying binding affinity. The structure complementarity between protein-binding pocket and ligand has a great effect on the binding strength between a protein and a ligand, but most of existing deep learning approaches usually extracted the features of pocket and ligand by these two detached modules. In this work, a new deep learning approach based on the cross-attention mechanism named CAPLA was developed for improved prediction of protein-ligand binding affinity by learning features from sequence-level information of both protein and ligand. Specifically, CAPLA employs the cross-attention mechanism to capture the mutual effect of protein-binding pocket and ligand. We evaluated the performance of our proposed CAPLA on comprehensive benchmarking experiments on binding affinity prediction, demonstrating the superior performance of CAPLA over state-of-the-art baseline approaches. Moreover, we provided the interpretability for CAPLA to uncover critical functional residues that contribute most to the binding affinity through the analysis of the attention scores generated by the cross-attention mechanism. Consequently, these results indicate that CAPLA is an effective approach for binding affinity prediction and may contribute to useful help for further consequent applications. The source code of the method along with trained models are freely available at https://github.com/lennylv/CAPLA. Supplementary data are available at Bioinformatics online.

Spiking neural P (SN P) systems are a class of discrete neuron-inspired computation models, where information is encoded by the numbers of spikes in neurons and the timing of spikes. However, due to the discontinuous nature of the integrate-and-fire behavior of neurons and the symbolic representation of information, SN P systems are incompatible with the gradient descent-based training algorithms, such as the backpropagation algorithm, and lack the capability of processing the numerical representation of information. In this work, motivated by the numerical nature of numerical P (NP) systems in the area of membrane computing, a novel class of SN P systems is proposed, called numerical SN P (NSN P) systems. More precisely, information is encoded by the values of variables, and the integrate-and-fire way of neurons and the distribution of produced values are described by continuous production functions. The computation power of NSN P systems is investigated. We prove that NSN P is Turing universal as number generating devices, where the production functions in each neuron are linear functions, each involving at most one variable; as number accepting devices, NSN P systems are proved to be universal as well, even if each neuron contains only one production function. These results show that even if a single neuron is simple in the sense that it contains one or two production functions and the production functions in each neuron are linear functions with one variable, a network of simple neurons are still computationally powerful. With the powerful computation power and the characteristic of continuous production functions, developing learning algorithms for NSN P systems is potentially exploitable.

Binding of peptides to major histocompatibility complex (MHC) molecules plays a crucial role in triggering T cell recognition mechanisms essential for immune response. Accurate prediction of MHC–peptide binding is vital for the development of cancer therapeutic vaccines. While recent deep learning-based methods have achieved significant performance in predicting MHC–peptide binding affinity, most of them separately encode MHC molecules and peptides as inputs, potentially overlooking critical interaction information between the two. In this work, we propose RPEMHC, a new deep learning approach based on residue–residue pair encoding to predict the binding affinity between peptides and MHC, which encode an MHC molecule and a peptide as a residue–residue pair map. We evaluate the performance of RPEMHC on various MHC-II-related datasets for MHC–peptide binding prediction, demonstrating that RPEMHC achieves better or comparable performance against other state-of-the-art baselines. Moreover, we further construct experiments on MHC-I-related datasets, and experimental results demonstrate that our method can work on both two MHC classes. These extensive validations have manifested that RPEMHC is an effective tool for studying MHC–peptide interactions and can potentially facilitate the vaccine development. The source code of the method along with trained models is freely available at https://github.com/lennylv/RPEMHC.

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.