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Encounter Complexes in Protein-Protein Association

Acpharis's scientists published an exciting paper in eLife today on using Acpharis's protein-protein docking program, Piper, to model encounter complexes in protein-protein association. While crystal structures provide a static image of proteins interacting, which can be useful in optimizing biologics design, understanding the association pathway to this complex is equally important for obtaining a full picture of the physical basis of complex formation.

Using Piper, the intermediate states of binding were predicted by keeping slightly higher energy structures. Rather than looking at the top 1,000 poses, as is traditionally done with docking using Piper, the top 10,000 poses were examined. When compared to experimental results using paramagnetic relaxation, high agreement between computational modeling and experiments were found.

Using this method, Acpharis's scientists were also able to find that protein-protein association pathways are primarily two-dimensional, a significant reduction from the six-dimensional space explored in rigid docking simulations. This reduced dimensional space can be more thoroughly explored for optimization of therapeutics.

Acpharis plans to continue work on using this modeling to further improve docking and the use of Acpharis's software for optimization of protein therapeutics.