In Silico Binding Assay: Molecular Dynamics For Binding Mode Prediction

In-Silico Binding Assay (ISBA)

When virtual screening is not enough, ISBA allows the reconstruction of the entire binding process of a ligand to its target,  capturing the formation of water bridges and networks, induced-fit effects, and the opening of cryptic pockets. In a collaboration with Pfizer, ISBA succeded in resolving the binding process where docking failed to produce a pose that could explain the behavior of some mutants.

With our in silico approach, we can sample the binding mode of a ligand to its target in a reasonable amount of time (days). Useful to obtain:

• Binding modes and pathways with Molecular Dynamics.
• Predict the binding kinetics (K_off and _Kon) of your ligand.
• Run unbinding simulations to evaluate pose stability.

Use Cases

• Rational drug design: Knowing the binding mode of your ligand is the first step towards structure-based design and lead-optimization.
• Patent reverse engineering: Although patents disclose the 2D structure of the compound and the target to which it binds, its binding mode might not necessarily be disclosed. We can help you find it.
• Estimate binding affinity and kinetics: One of the key properties of a drug is its binding affinity. We can estimate K_D, K_on and K_off values with Markov state models.
• Binding pathway: In addition to the binding mode, you will obtain the pathway that the ligand follows from bulk to bound state.

Results

• A PlayMolecule scene with binding mode predictions and binding pathway.
• The full simulations (.xtc and .pdb files).
• An extensive report summarizing the structural insights obtained.

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