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I read that the Protein-Protein interactions one can consider are generally of two types, namely physical and functional, but I cannot get the difference between the two.

I was just thinking that if two proteins are linked in a Protein-Protein interaction network like the ones stored in STRING database, then they are experimentally observed or somehow predicted to physically interact through binding sites to explicitly perform a function, e.g. signal transduction. But as I am reading different sources making the separation between the two kinds of interactions I got a little bit puzzled.

Can you please help me?

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  • $\begingroup$ What on earth is "I got the PPIs" supposed to mean? And what is "a PPIN like STRING"? If you are going to post on this site you must take the trouble to define all acronyms (other than DNA etc) and express yourself clearly. Otherwise your question will be thown out as unclear. $\endgroup$ – David Feb 28 '17 at 20:56
  • $\begingroup$ PPIN: Protein-Protein Interaction Network, STRING: one of the largest and more used database related to such networks. I'm sorry for the inconvenience, I thought the acronyms were known. Now the question should be more clear. $\endgroup$ – Noired Feb 28 '17 at 23:49
  • $\begingroup$ Thank you, but definitions belong in questions. Please edit your question. $\endgroup$ – David Feb 28 '17 at 23:52
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    $\begingroup$ Done, I hope now it's more understandable. $\endgroup$ – Noired Feb 28 '17 at 23:57
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As I understand it, "physical" and "functional" are just two different ways of analyzing an interaction between proteins. Proteins can and do interact physically, meaning they can bind in specific ways and sites, and this binding can produce changes in those same proteins (like conformational changes), which alter their properties. This is the purely physical analysis of the protein interaction. The functional analysis begins when we ask the questions "What is the role that this interaction performs in the cell/organism/living system?"; "What effects do these changes in the protein are going to create in the cell/organism/living system?". Often a conformational change in a protein induced by an interaction with another activates or inactivates it. In other words, an interaction can create a conformational change that enables (activation) or disables (inactivation) the protein to catalyze a given reaction, and so the referred interaction plays an important function in regulating the protein's activity. For instance, phagocytes (cells capable of phagocytosis) have in their membranes proteins capable of physically interacting with proteins present in pathogens membranes. They physically bind to them, changing their conformation in the process. This is the physical part of the interaction, it is what happens purely physically (and can be studied more deeply). This conformational change will enable the protein to catalyze a series of reactions inside the phagocytic cell that will ultimately lead to the phagocytosis and destruction of the pathogen. This is the functional analysis of the interaction, it is understanding what is functionally achieved by the interaction, in this case enabling phagocytosis (and can be studied more deeply).

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