KASSPer: Kinase Active Site Structure Prediction using Protein and Ligand Language Models and Its Application to Virtual Screening.

Abstract

Structure-based virtual screening (SBVS) is limited by the rigid-receptor assumption, which is particularly problematic for kinases that adopt multiple active-site conformations but are experimentally biased toward a single state. Although ensemble screening can address this limitation, it remains computationally expensive. We introduce KASSPer (Kinase Active Site Structure Predictor), a framework that predicts kinase active-site conformational states using protein and compound language models. Given a kinase amino acid sequence and a ligand SMILES string, KASSPer enables ligand-specific conformer selection prior to SBVS, potentially reducing the computational cost associated with exhaustive ensemble screening. Benchmarking on the DUD-E kinase subset demonstrates that KASSPer-guided screening outperforms the tested ensemble-based approach across the evaluation metrics. The implementation for model loading and inference is available at the GitHub repository https://github.com/kucm-lsbi/KASSPer. Supplementary data are available at Bioinformatics online.