Abstract
Sodium transporters maintain cellular homeostasis by transporting ions, minerals, and nutrients across the membrane, and Na+/K+ ATPases facilitate the cotransport of solutes in neurons, muscle cells, and epithelial cells. Sodium transporters are important for many physiological processes, and their dysfunction leads to diseases such as hypertension, diabetes, neurological disorders, and cancer. The NA_mCNN computational method highlights the functional diversity and significance of sodium transporters in membrane proteins using protein language model embeddings (PLMs) and multiple-window scanning deep learning models. This work investigates PLMs that include Tape, ProtTrans, ESM-1b-1280, and ESM-2-128 to achieve more accuracy in sodium transporter classification. Five-fold cross-validation and independent testing demonstrate ProtTrans embedding robustness. In cross-validation, ProtTrans achieved an AUC of 0.9939, a sensitivity of 0.9829, and a specificity of 0.9889, demonstrating its ability to distinguish positive and negative samples. In independent testing, ProtTrans maintained a sensitivity of 0.9765, a specificity of 0.9991, and an AUC of 0.9975, which indicates its high level of discrimination. This study advances the understanding of sodium transporter diversity and function, as well as their role in human pathophysiology. Our goal is to use deep learning techniques and protein language models for identifying sodium transporters to accelerate identification and develop new therapeutic interventions.