Wrap n Shake

Wrap n Shake predicts atomic-resolution multiple ligand binding sites on macromolecular targets to support drug design.

Key Features:

• Atomic Resolution Mapping: Wrap n Shake systematically maps binding sites by wrapping the entire target surface with a monolayer of ligand molecules to ensure comprehensive coverage.
• Addresses Limitations of Blind Docking: It mitigates issues arising from approximations in hydration models, simplified molecular flexibility handling, and imperfect search algorithms associated with blind docking.
• Molecular Dynamics Integration: The method uses rapid molecular dynamics simulations to "shake" wrapped ligand molecules and identify functional binding sites through dynamic interactions.

Scientific Applications:

• Drug design and discovery: Identification and characterization of multiple prerequisite or allosteric binding sites on targets relevant to drug development.
• Mitogen-Activated Protein Kinases: Method tested on these key regulators of cellular signaling pathways.
• Tyrosine-Protein Kinases: Method tested on these enzymes involved in signal transduction mechanisms.
• Farnesyl Pyrophosphate Synthase: Method tested on this target relevant to the development of antitumor agents.

Methodology:

Two-step computational process: a wrapping phase that envelops the entire macromolecular surface with ligand molecules, followed by a shaking phase using rapid molecular dynamics simulations to refine interactions and extract functional binding sites.