Determination of locked interfaces in biomolecular complexes using Haptimol_RD

Area of Science:

• Biochemistry and Structural Biology
• Computational Biology
• Human-Computer Interaction

Background:

• Molecular complex formation is crucial for biological processes.
• Understanding protein-protein interactions is key to drug discovery and disease research.
• Virtual environments offer novel approaches to studying molecular interactions.

Purpose of the Study:

• To investigate the utility of interactive haptics-assisted docking for studying protein complex formation.
• To differentiate between protein interfaces that allow rigid-body docking and those that require conformational changes.
• To introduce the concept of locked versus non-locked protein interfaces based on docking behavior.

Main Methods:

• Utilized Haptimol_RD, a haptics software tool, for rigid docking simulations.
• Assessed the docking of four protein dimers (homo and hetero) with separated subunits.
• Classified dimer interfaces as interwinding or non-interwinding based on their geometry.

Main Results:

• Successfully docked protein dimers with non-interwinding interfaces using rigid-body movements.
• Failed to dock dimers with interwinding interfaces, indicating a need for conformational changes.
• Observed a haptic "sucking" effect at the correct binding pose for successfully docked dimers, correlating with interaction energy minima.

Conclusions:

• Protein interfaces can be classified as locked or non-locked based on their requirement for intra-subunit conformational changes during docking.
• Non-locked interfaces facilitate straightforward docking via rigid-body movements.
• Locked interfaces necessitate conformational adjustments within subunits for complex formation, impacting biological function and therapeutic targeting.