Contact-Assisted Threading in Low-Homology Protein Modeling

The ability to successfully predict the three-dimensional structure of a protein from its amino acid sequence has made considerable progress in the recent past. The progress is propelled by the improved accuracy of deep learning-based inter-residue contact map predictors coupled with the rising growth of protein sequence databases. Contact map encodes interatomic interaction information that can be exploited for highly accurate prediction of protein structures via contact map threading even for the query proteins that are not amenable to direct homology modeling. As such, contact-assisted threading has garnered considerable research effort. In this chapter, we provide an overview of existing contact-assisted threading methods while highlighting the recent advances and discussing some of the current limitations and future prospects in the application of contact-assisted threading for improving the accuracy of low-homology protein modeling.