SPIRED-Fitness: an end-to-end framework for the prediction of protein structure and fitness from single sequence

AO_SCPLOWBSTRACTC_SCPLOWSignificant research progress has been made in the field of protein structure and fitness prediction. Particularly, single-sequence-based structure prediction methods like ESMFold and OmegaFold achieve a balance between inference speed and prediction accuracy, showing promise for many downstream prediction tasks. Here, we propose SPIRED, a novel single-sequence-based structure prediction model that exhibits comparable performance to the state-of-the-art methods but with approximately 5-fold acceleration in inference and at least one order of magnitude reduction in training consumption. By integrating SPIRED with downstream neural networks, we compose an end-to-end framework named SPIRED-Fitness for the rapid prediction of both protein structure and fitness from single sequence. SPIRED-Fitness and its derivative SPIRED-Stab achieve state-of-the-art performance in predicting the mutational effects on protein fitness and stability metrics, respectively.