biostudies-literatureUnknown43(6)Narang KSalt-tolerant proteins, also known as halophilic proteins, have unique adaptations to function in high-salinity environments. These proteins have naturally evolved in extremophilic organisms, and more recently, are being increasingly applied as enzymes in industrial processes. Due to an abundance of salt-tolerant sequences and a simultaneous lack of experimental structures, most computational methods to predict stability are sequence-based only. These approaches, however, are hindered by a lack of structural understanding of these proteins. Here, we present HaloClass, an SVM classifier that leverages ESM-2 protein language model embeddings to accurately identify salt-tolerant proteins. On a newer and larger test dataset, HaloClass outperforms existing approaches when predicting the stabiliThe protein journal1035-1044https://www.ebi.ac.uk/biostudies/studies/S-EPMC11543744biostudies-literatureHaloClass: Salt-Tolerant Protein Classification with Protein Language Models.PMC11543744Chu SKSHemstrom WNarang KNath AfalseHaloClass: Salt-Tolerant Protein Classification with Protein Language Models.Salt-tolerant proteins, also known as halophilic proteins, have unique adaptations to function in high-salinity environments. These proteins have naturally evolved in extremophilic organisms, and more recently, are being increasingly applied as enzymes in industrial processes. Due to an abundance of salt-tolerant sequences and a simultaneous lack of experimental structures, most computational methods to predict stability are sequence-based only. These approaches, however, are hindered by a lack of structural understanding of these proteins. Here, we present HaloClass, an SVM classifier that leverages ESM-2 protein language model embeddings to accurately identify salt-tolerant proteins. On a newer and larger test dataset, HaloClass outperforms existing approaches when predicting the stabili2024-01-01T00:00:00Z2024 Dec2026-06-02T22:07:35.631Z2025-04-04T02:58:25.033ZS-EPMC115437443943217510.1007/s10930-024-10236-7