No abstract

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to biology due to the rise in available data. We attempt to link protein design and deep learning by using variational autoencoders to generate protein sequences conditioned on desired properties. Potential copper and calcium binding sites are added to non-metal binding proteins without human intervention and compared to a hidden Markov model. In another use case, a grammar of protein structures is developed and used to produce sequences for a novel protein topology. One candidate structure is found to be stable by molecular dynamics simulation. The ability of our model to confine the vast search space of protein sequences and to scale easily has the potential to assist in a variety of protein design tasks.

Motivation Over the past 50 years, our ability to model protein sequences with evolutionary information has progressed in leaps and bounds. However, even with the latest deep learning methods, the modelling of a critically important class of proteins, single orphan sequences, remains unsolved. Results By taking a bioinformatics approach to semi-supervised machine learning, we develop Profile Augmentation of Single Sequences (PASS), a simple but powerful framework for building accurate single-sequence methods. To demonstrate the effectiveness of PASS we apply it to the mature field of secondary structure prediction. In doing so we develop S4PRED, the successor to the open-source PSIPRED-Single method, which achieves an unprecedented Q3 score of 75.3% on the standard CB513 test. PASS provides a blueprint for the development of a new generation of predictive methods, advancing our ability to model individual protein sequences. Availability The S4PRED model is available as open source software on the PSIPRED GitHub repository (https://github.com/psipred/s4pred), along with documentation. It will also be provided as a part of the PSIPRED web service (http://bioinf.cs.ucl.ac.uk/psipred/) Supplementary information Supplementary data are available at Bioinformatics online.