Integrative modeling of diverse protein-peptide systems using CABS-dock

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• The CABS model is versatile for protein-protein and protein-peptide molecular modeling.
• Tasks include simulating folding, structure prediction, docking, and analyzing molecular complex dynamics.

Purpose of the Study:

• To apply the CABS-dock tool to predict amyloid protofilament structures.
• To identify cleavage sites in peptide substrates of proteolytic enzymes using CABS-dock.

Main Methods:

• Simultaneous docking simulations of amyloidogenic peptides.
• Utilizing CABS-dock coarse-grained docking simulations for enzyme-substrate interactions.
• Scoring models using symmetry criteria and interaction energy.

Main Results:

• CABS model accurately predicted amyloid protofilament structures (in-register parallel architecture) for 5 out of 6 systems.
• Correctly identified cleavage sites in 12 out of 15 analyzed peptide substrates.
• Generated atomic structures of enzyme-substrate complexes.

Conclusions:

• CABS-dock is effective for predicting amyloid protofilament structures.
• CABS-dock aids in identifying proteolytic cleavage sites, especially when combined with sequence-based methods.
• The method offers insights into enzyme-substrate interactions for inhibitor design.