In Silico Conformational Assay: Molecular Dynamics To Study Protein Flexibility

4D structure prediction

The Conformational Landscape

While crystal structures can help enormously in understanding your target, they only offer a static picture, a small well of the conformational landscape of your target.

With HTMD adaptive sampling protocol, we can study the conformational landscape of a protein efficiently, revealing structural insights which can directly impact a drug discovery campaign.

Case Study

With molecular dynamics, we can further explore this landscape, visiting other relevant wells, such as the active conformation of a GPCR, or the DFG-out conformation of a kinase. In collaboration with UCB, we transitioned the structure of a GPCR from its inactive to its active conformation, using unbiased simulations.

  • Unique structural insights: Knowing the different conformations that your target can adopt can give you an edge.
  • Ensemble docking: Build an ensemble of pocket conformations to do ensemble docking.
  • Understanding transitions: Visualize how a virus spike protein adopts the host-bound-ready state or how a GPCR goes from inactive to active.
  • Estimate conformational stability: Is a particular mutant more likely to stay in a given conformation than the wild-type?


  • A PlayMolecule scene including the most prominent conformations and relevant structural changes.
  • The full simulations (.xtc and .pdb files).
  • A report summarizing the structural insights obtained.
  • Direct communication with the team to discuss the results.

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