ContactLib-ATT: A Structure-Based Search Engine for Homologous Proteins

IEEE/ACM Trans Comput Biol Bioinform. 2023 Nov-Dec;20(6):3421-3429. doi: 10.1109/TCBB.2022.3197802. Epub 2023 Dec 25.

Abstract

General-purpose protein structure embedding can be used for many important protein biology tasks, such as protein design, drug design and binding affinity prediction. Recent researches have shown that attention-based encoder layers are more suitable to learn high-level features. Based on this key observation, we propose a two-level general-purpose protein structure embedding neural network, called ContactLib-ATT. On local embedding level, a biologically more meaningful contact context is introduced. On global embedding level, attention-based encoder layers are employed for better global representation learning. Our general-purpose protein structure embedding framework is trained and tested on the SCOP40 2.07 dataset. As a result, ContactLib-ATT achieves a SCOP superfamily classification accuracy of 82.4% (i.e., 6.7% higher than state-of-the-art method). On the same dataset, ContactLib-ATT is used to simulate a structure-based search engine for remote homologous proteins, and our top-10 candidate list contains at least one remote homolog with a probability of 91.9%.

MeSH terms

  • Neural Networks, Computer
  • Proteins* / chemistry
  • Search Engine*

Substances

  • Proteins