SELFprot: Effective and Efficient Multitask Finetuning Methods for Protein Parameter Prediction.

Abstract

Accurately predicting protein-ligand interactions and enzymatic kinetics remains a challenge for computational biology. Here, we present SELFprot, a suite of modular transformer-based machine learning architectures that leverage the ESM2-35M model architecture for protein sequence and small molecule embeddings to improve predictions of complex biochemical interactions. SELFprot employs multitask learning and parameter-efficient finetuning through low-rank adaptation, allowing for adaptive, data-driven model refinement. Furthermore, ensemble learning techniques are used to enhance the robustness and reduce the prediction variance. Evaluated on the BindingDB and CatPred-DB data sets, SELFprot achieves competitive performance with notable improvements in parameter-efficient prediction of k_cat, K_m, K_i, K_d, IC₅₀, and EC₅₀ values as well as the classification of functional site residues. With comparable accuracy to existing models and an order of magnitude fewer parameters, SELFprot demonstrates versatility and efficiency, making it a valuable tool for protein-ligand interaction studies in bioengineering.