BiMba: using Vision Mamba to predict protein sites that bind other proteins

Abstract

Abstract Motivation Identifying protein binding sites in protein–protein complexes is a central challenge in structural biology. Binding sites, consisting of groups of residues, govern how proteins recognize, and interact with protein partners. Thus, identifying them is essential for understanding biological function and guiding the design of effective biomolecules and even drug molecules. Despite major progress in computational approaches, their performance remains limited because most models underrepresent the combined influence of surface properties and residue-level information, leaving room for improvement. Recent advances in state-space models and vision-based deep learning offer an opportunity to address these limitations by efficiently modeling long-range spatial dependencies on protein surfaces. Here, we introduce BiMba (protein Binding site prediction using Vision Mamba), a state-space–driven deep learning framework that leverages the efficient long-range modeling capability of the Vision Mamba architecture to learn from three-dimensional (3D) protein surfaces represented as two-dimensional (2D) geometric or physicochemical grids. Results BiMba integrates complementary sources of information, capturing geometric and physicochemical determinants of molecular recognition as surface patches, encoded as 2D images, along with residue-level descriptors, yielding a unified representation that couples spatial topology with biochemical context. BiMba demonstrates competitive performance across diverse and specialized benchmark datasets, often outperforming existing state-of-the-art methods. In addition, BiMba incorporates perturbation-based and gradient-based interpretability analyses by extracting hidden attentions from Mamba layers, enabling visualization of feature relevance and biologically meaningful residue clusters. Overall, our findings establish state-space models as efficient, interpretable, and scalable architectures for molecular surface learning, advancing the application of deep learning in structural bioinformatics. Availability and implementation The BiMba source code, training, test, and benchmark datasets are available at https://github.com/Azam-Shi/BiMba.