Single-Sequence-Based Protein Secondary Structure Prediction using One-Hot and Chemical Encodings of Amino Acids

Abstract: In protein secondary structure prediction, each amino acid in sequence is typically treated as a distinct category and represented by a one-hot vector. In this study, we developed two novel chemical representations for amino acids utilizing molecular fingerprints and the dimensionality reduction algorithm FastMap. We demonstrate that the two new chemical encodings can provide additional information about the interactions of amino acids in sequences that an LSTM-based model cannot capture with one-hot encoding alone. Compared to the latest LSTM-based model used in the single-sequence-based method SPOT-1D-Single, our ensemble model utilizing one-hot and chemical encodings achieves better accuracy across most test sets while requiring approximately nine times fewer trainable parameters for each encoding model. Our single-sequence-based method is valuable for its simplicity, lower resource requirements, and independence from external sequence data. It is beneficial when quick or preliminary predictions are needed or when data on homologous sequences is scarce.