H-bond network optimization in protein-protein complexes: are all-atom force field scores enough?

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Predicting protein-protein complex structures from unbound states is challenging.
• Distinguishing true positives from false positives in docking is a major hurdle.

Purpose of the Study:

• To develop a hierarchical protocol for protein-protein docking refinement.
• To improve the discrimination of near-native poses from docking candidates.

Main Methods:

• Combines efficient sampling of hydrogen bond networks and side chains.
• Utilizes an all-atom force field and a surface generalized Born implicit solvent model.
• Tested on 22 protein complexes with known near-native solutions.

Main Results:

• Achieved a near-native solution as the top pose in 70% of tested cases.
• The method identified near-native solutions within the top 100 docking poses for all complexes.
• Optimized hydrogen bond networks with all-atom force fields significantly enhance scoring functions.

Conclusions:

• The hierarchical docking refinement protocol effectively discriminates near-native protein-protein complex structures.
• All-atom force fields and optimized hydrogen bond networks represent a significant advancement in protein docking accuracy.