FReDoWS: a method to automate molecular docking simulations with explicit receptor flexibility and snapshots...

Area of Science:

• Computational chemistry
• Drug discovery
• Biophysics

Background:

• Molecular docking is crucial for structure-based drug design.
• Traditional methods often treat receptors as rigid, ignoring their inherent flexibility.
• Accounting for macromolecular flexibility in docking is challenging but essential for accurate modeling.

Purpose of the Study:

• To develop an automated workflow system for molecular docking simulations using fully-flexible receptor models.
• To accelerate virtual screening by incorporating a snapshot selection feature.
• To investigate the role of receptor flexibility in ligand binding.

Main Methods:

• Development of the Flexible-Receptor Docking Workflow System (FReDoWS).
• Implementation of a snapshot selection feature for accelerated virtual screening.
• Application of FReDoWS to dock ligands to flexible models of Mycobacterium tuberculosis InhA enzyme and its mutants.

Main Results:

• FReDoWS successfully automates complex molecular docking simulations.
• The snapshot selection feature accelerates virtual screening processes.
• All four tested ligands demonstrated effective binding to the flexible InhA models, consistent with experimental data.

Conclusions:

• FReDoWS automates labor-intensive computational tasks in molecular docking.
• The system's user-friendly interface allows parameter customization.
• FReDoWS facilitates the exploration of flexibility's role in receptor-ligand interactions and can be made available upon request.