SeaMoon: Prediction of molecular motions based on language models

How protein move and deform determines their interactions with the environment and is thus of utmost importance for cellular functioning. Following the revolution in single protein 3D structure prediction, researchers have focused on repurposing or developing deep learning models for sampling alternative protein conformations. In this work, we explored whether continuous compact representations of protein motions could be predicted directly from protein sequences, without exploiting nor sampling protein structures. Our approach, called SeaMoon, leverages protein Language Model (pLM) embeddings as input to a lightweight ( ∼ 1M trainable parameters) convolutional neural network. SeaMoon achieves a success rate of up to 40% when assessed against ∼ 1 000 collections of experimental conformations exhibiting a wide range of motions. SeaMoon capture motions not accessible to the normal mode analysis, an unsupervised physics-based method relying solely on a protein structure’s 3D geometry, and generalises to proteins that do not have any detectable sequence similarity to the training set. SeaMoon is easily retrainable with novel or updated pLMs.