Modeling beta-sheet peptide-protein interactions: Rosetta FlexPepDock in CAPRI rounds 38-45

Area of Science:

• Structural biology
• Computational chemistry
• Biophysics

Background:

• Peptide-protein interactions are crucial in biological processes.
• Peptide docking is complex due to peptide flexibility.
• Beta-sheet complementation is a unique interaction mode involving main chain hydrogen bonds.

Purpose of the Study:

• To evaluate and enhance peptide docking protocols for beta-sheet complementation.
• To model challenging peptide-protein interactions accurately.
• To understand the structural basis of binding affinity and specificity in beta-sheet complementation.

Main Methods:

• Utilized the Rosetta FlexPepDock protocol for peptide docking.
• Applied the PIPER-FlexPepDock protocol to the PeptiDBeta benchmark dataset.
• Tested the protocol on CAPRI targets 134, 135, and T121.

Main Results:

• Achieved high-accuracy models for L-MAG/DLC8 interactions (targets 134, 135).
• Generated the only medium-accuracy models for the challenging target T121.
• Demonstrated that the peptide beta-strand is key for modeling, with adjacent residues refining accuracy.

Conclusions:

• The PIPER-FlexPepDock protocol effectively models beta-sheet complementation peptide-protein interactions.
• Beta-strand formation is critical for accurate peptide docking in this mode.
• Incorporating adjacent peptide residues enhances model resolution and reliability.