CollagenTransformer: End-to-End Transformer Model to Predict Thermal Stability of Collagen Triple Helices Using an NLP Approach.

Abstract

Collagen is one of the most important structural proteins in biology, and its structural hierarchy plays a crucial role in many mechanically important biomaterials. Here, we demonstrate how transformer models can be used to predict, directly from the primary amino acid sequence, the thermal stability of collagen triple helices, measured via the melting temperature Tm. We report two distinct transformer architectures to compare performance. First, we train a small transformer model from scratch, using our collagen data set featuring only 633 sequence-to-Tm pairings. Second, we use a large pretrained transformer model, ProtBERT, and fine-tune it for a particular downstream task by utilizing sequence-to-Tm pairings, using a deep convolutional network to translate natural language processing BERT embeddings into required features. Both the small transformer model and the fine-tuned ProtBERT model have similar R2 values of test data (R2 = 0.84 vs 0.79, respectively), but the ProtBERT is a much larger pretrained model that may not always be applicable for other biological or biomaterials questions. Specifically, we show that the small transformer model requires only 0.026% of the number of parameters compared to the much larger model but reaches almost the same accuracy for the test set. We compare the performance of both models against 71 newly published sequences for which Tm has been obtained as a validation set and find reasonable agreement, with ProtBERT outperforming the small transformer model. The results presented here are, to our best knowledge, the first demonstration of the use of transformer models for relatively small data sets and for the prediction of specific biophysical properties of interest. We anticipate that the work presented here serves as a starting point for transformer models to be applied to other biophysical problems.