SPOT-1D-LM: Reaching Alignment-profile-based Accuracy in Predicting Protein Secondary and Tertiary Structural Properties without Alignment

ABSTRACT Protein language models have emerged as an alternative to multiple sequence alignment for enriching sequence information and improving downstream prediction tasks such as biophysical, structural, and functional properties. Here we show that a combination of traditional one-hot encoding with the embeddings from two different language models (ProtTrans and ESM-1b) allows a leap in accuracy over single-sequence based techniques in predicting protein 1D secondary and tertiary structural properties, including backbone torsion angles, solvent accessibility and contact numbers. This large improvement leads to an accuracy comparable to or better than the current state-of-the-art techniques for predicting these 1D structural properties based on sequence profiles generated from multiple sequence alignments. The high-accuracy prediction in both secondary and tertiary structural properties indicates that it is possible to make highly accurate prediction of protein structures without homologous sequences, the remaining obstacle in the post AlphaFold2 era.