Searching for protein variants with desired properties using deep generative models

Abstract

Background: Protein engineering aims to improve the functional properties of existing proteins to meet people’s needs. Current deep learning-based models have captured evolutionary, functional, and biochemical features contained in amino acid sequences. However, the existing generative models need to be improved when capturing the relationship between amino acid sites on longer sequences. At the same time, the distribution of protein sequences in the homologous family has a specific positional relationship in the latent space. We want to use this relationship to search for new variants directly from the vicinity of better-performing varieties. Results: To improve the representation learning ability of the model for longer sequences and the similarity between the generated sequences and the original sequences, we propose a temporal variational autoencoder (T-VAE) model. T-VAE consists of an encoder and a decoder. The encoder expands the receptive field of neurons in the network structure by dilated causal convolution, thereby improving the encoding representation ability of longer sequences. The decoder decodes the sampled data into variants closely resembling the original sequence. Conclusion: Compared to other models, the person correlation coefficient between the predicted values of protein fitness obtained by T-VAE and the truth values was higher, and the mean absolute deviation was lower. In addition, the T-VAE model has a better representation learning ability for longer sequences when comparing the encoding of protein sequences of different lengths. These results show that our model has more advantages in representation learning for longer sequences. To verify the model’s generative effect, we also calculate the sequence identity between the generated data and the input data. The sequence identity obtained by T-VAE improved by 12.9% compared to the baseline model.