DRLComplex: Reconstruction of protein quaternary structures using deep reinforcement learning

Predicted inter-chain residue-residue contacts can be used to build the quaternary structure of protein complexes from scratch. However, only a small number of methods have been developed to reconstruct protein quaternary structures using predicted inter-chain contacts. Here, we present an agent-based self-learning method based on deep reinforcement learning (DRLComplex) to build protein complex structures using inter-chain contacts as distance constraints. We rigorously tested DRLComplex on two standard datasets of homodimeric and heterodimeric protein complexes (i.e., the CASP-CAPRI homodimer and Std_32 heterodimer datasets) using both true and predicted interchain contacts as inputs. Utilizing true contacts as input, DRLComplex achieved high average TM-scores of 0.9895 and 0.9881 and a low average interface RMSD (I_RMSD) of 0.2197 and 0.92 on the two datasets, respectively. When predicted contacts are used, the method achieves TM-scores of 0.73 and 0.76 for homodimers and heterodimers, respectively. Our experiments find that the accuracy of reconstructed quaternary structures depends on the accuracy of the contact predictions. Compared to other optimization methods for reconstructing quaternary structures from inter-chain contacts, DRLComplex performs similar to an advanced gradient descent method and better than a Markov Chain Monte Carlo simulation method and a simulated annealing-based method, validating the effectiveness of DRLComplex for quaternary reconstruction of protein complexes.