Biology subjects

Soltanikazemi, E.

Publications and source records attributed to Soltanikazemi, E..

3 recordsLinked to original sources

bioRxiv2022

A deep reinforcement learning approach to reconstructing quaternary structures of protein dimers through self-learning

Predicted interchain 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 interchain contacts. Here, we present an agent-based self-learning method based on deep reinforcement learning (DRLComplex) to build protein complex structures using interchain contacts as distance constraints. We rigorously tested the DRLComplex on two standard datasets of homodimeric and heterodimeric dimers (the CASP-CAPRI homodimer dataset and Std_32 heterodimer dataset) using both true and predicted contacts. Utilizing true contacts as input, the DRLComplex achieved a high average TM-score 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 the TM-score of 0.73 and 0.76 for homodimers and heterodimers respectively. The accuracy of reconstructed quaternary structures depends on the accuracy of contact predictions. Compared with other optimization methods of reconstructing quaternary structures from interchain contacts, DRLComplex performs similarly to an advanced gradient descent method and better than a Markov Chain Monte Carlo simulation method and a simulated annealing-based method. The source code of DRLComplex is available at: https://github.com/jianlin-cheng/DRLComplex

bioinformatics↗

bioRxiv2021

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

MotivationDeep 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. ResultsTested 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. AvailabilityThe source code of DRCon is available at https://github.com/jianlin-cheng/DRCon. Contactchengji@missouri.edu

bioinformatics↗

bioRxiv2021

Distance-based Reconstruction of Protein Quaternary Structures from Inter-Chain Contacts

Predicting the quaternary structure of a protein complex is an important and challenging problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures of protein complexes. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we introduce a new gradient descent optimization algorithm (GD) to build quaternary structures of protein dimers utilizing inter-chain contacts as distance restraints. We evaluate GD on several datasets of homodimers and heterodimers using true or predicted contacts. GD consistently performs better than a simulated annealing method and a Markov Chain Monte Carlo simulation method. Using true inter-chain contacts as input, GD can reconstruct high-quality structural models for homodimers and heterodimers with average TM-score ranging from 0.92 to 0.99 and average interface root mean square distance (I-RMSD) from 0.72 [A] to 1.64 [A]. On a dataset of 115 homodimers, using predicted inter-chain contacts as input, the average TM-score of the structural models built by GD is 0.76. For 46% of the homodimers, high-quality structural models with TM-score >= 0.9 are reconstructed from predicted contacts. There is a strong correlation between the quality of the reconstructed models and the precision and recall of predicted contacts. If the precision or recall of predicted contacts is >20%, GD can reconstruct good models for most homodimers, indicating only a moderate precision or recall of inter-chain contact prediction is needed to build good structural models for most homodimers. Moreover, the accuracy of reconstructed models positively correlates with the contact density in dimers and depends on the initial model and the probability threshold of selecting predicted contacts for the distance-based structure optimization.

bioinformatics↗