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