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Distance-based Reconstruction of Protein Quaternary Structures from Inter-Chain Contacts
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  • Elham Soltanikazemi,
  • Farhan Quadir,
  • Raj Roy,
  • Jianlin Cheng
Elham Soltanikazemi
University of Missouri

Corresponding Author:[email protected]

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Farhan Quadir
University of Missouri
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Raj Roy
University of Missouri
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Jianlin Cheng
University of Missouri
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Predicting the quaternary structure of protein complex is an important problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we introduce a 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 Å to 1.64 Å. 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.
17 Jul 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
20 Jul 2021Submission Checks Completed
20 Jul 2021Assigned to Editor
22 Jul 2021Reviewer(s) Assigned
06 Aug 2021Review(s) Completed, Editorial Evaluation Pending
07 Aug 2021Editorial Decision: Revise Major
25 Sep 20211st Revision Received
28 Sep 2021Submission Checks Completed
28 Sep 2021Assigned to Editor
28 Sep 2021Reviewer(s) Assigned
07 Oct 2021Review(s) Completed, Editorial Evaluation Pending
12 Oct 2021Editorial Decision: Accept
Mar 2022Published in Proteins: Structure, Function, and Bioinformatics volume 90 issue 3 on pages 720-731. 10.1002/prot.26269