I am studying protein-protein interactions. I have a question regarding this. If 2 proteins X and Y are binding and one of of the proteins is NAD+ dependent, then should the docking of X-NAD+ complex with Y be done or X can be directly docked with Y?
If one of the proteins in a protein-protein interaction has X-NAD+ dependency, docking should ideally be performed considering X and ADP-ribose together instead of just using protein X with Y, since the presence of NAD can affect the binding conformation and binding interface for Protein X.
Including NAD+ in the docking helps resolve specific conformers of protein X that are crucial for its interaction with Protein Y. This is especially important in dynamic systems involving multiple partners, as changes in structure can arise when complexes form. Docking the X-NAD+ complex ensures the interaction reflects the functional, biologically relevant form of protein X.
Hey Daniel Malu. Thanks for the reply. I still have a small query. ADP ribose is the reaction product, after X and Y binds. This is a deacetylation reaction in which X deacetylates Y. So, should X and ADP-ribose be docked with Y? Or X and NAD with Y?
In this case: ADP-ribose is the product of the reaction, and X deacetylates Y in the presence of NAD+. The relevant state for docking depends on which stage of your interaction you're considering:
1. When studying the initial interaction (before deacetylation), it would therefore be rational to dock X-NAD+ with Y. NAD+ is the substrate in this reaction, and docking X→NAD+:Y will provide insight into how X binds, ultimately leading to deacetylation.
2. Now, if we are considering the post-reaction state of Y proteins where deacetylation has taken place and ADP-ribose is formed as a product, you would dock the X-ADP-ribose complex with Y to understand how these proteins arrange themselves after the reaction. How do they interact now that the acetyl group is released, and only AMP and nicotinamide remain?
Therefore, Y should also be docked into the X-NAD+ complex if your interest is in observing how the enzymatic interaction results in deacetylation (pre-reaction). Finally, for a post-reaction complex, you will want to dock X with ADP-ribose.
Daniel Malu Thank you for the detailed explanation. I am quite interested in studying the binding sites between X-NAD+ with Y i.e. how they bind. Later I want to study the effect of a particular deleterious mutation in X that alters its binding with Y. From the above explanation, i understand that X-NAD+ with Y(pre-reaction).
You are welcome for suggestions in my study.
Daniel Malu Hey... I am facing one more issue. While I am docking X-NAD+ with Y through HDOCK and other docking servers, the docked complex doesn't show NAD+ in it. What can be the possible reason?
Hi, Daniel Malu I have one question regarding using alpha-fold structures in protein-protein docking. Do alpha-fold protein structures need to be stabilized by MD simulation before actually studying its interaction pattern with another protein?
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