A deep dilated convolutional residual network for predicting interchain contacts of protein homodimers

Motivation Deep learning has revolutionized protein tertiary structure prediction recently. The cutting-edge deep learning methods such as AlphaFold can predict high-accuracy tertiary structures for most individual protein chains. However, the accuracy of predicting quaternary structures of protein complexes consisting of multiple chains is still relatively low due to lack of advanced deep learning methods in the field. Because interchain residue-residue contacts can be used as distance restraints to guide quaternary structure modeling, here we develop a deep dilated convolutional residual network method (DRCon) to predict interchain residue-residue contacts in homodimers from residue-residue co-evolutionary signals derived from multiple sequence alignments of monomers, intrachain residue-residue contacts of monomers extracted from true/predicted tertiary structures or predicted by deep learning, and other sequence and structural features. Results Tested on three homodimer test datasets (Homo_std dataset, DeepHomo dataset, and CASP14-CAPRI dataset), the precision of DRCon for top L/5 interchain contact predictions (L: length of monomer in a homodimer) is 43.46%, 47.15%, and 24.81% respectively, which is substantially better than two existing deep learning interchain contact prediction methods. Moreover, our experiments demonstrate that using predicted tertiary structure or intrachain contacts of monomers in the unbound state as input, DRCon still performs reasonably well, even though its accuracy is lower than when true tertiary structures in the bound state are used as input. Finally, our case study shows that good interchain contact predictions can be used to build high-accuracy quaternary structure models of homodimers. Availability The source code of DRCon is available at https://github.com/jianlin-cheng/DRCon . Contact [email protected]