Protein-protein interactions are when two or more proteins bind together, possibly for some important biological function. Recently, I'm starting to look more into proteins, and in particular, networks related to proteins, such as protein-protein interaction networks. I found myself thinking about the following question:

Question: Does the relative size of two proteins significantly affect how likely they are to interact? Does it affect how they interact?

It would be plausible for me to download a protein-protein interaction network, and calculate their relative size from the proteins' PDB files. However, I predict that the results from such a computation would not offer much insight into why (or why not) the protein sizes affect binding.

  • $\begingroup$ Do you mean size in 3D space or mass? $\endgroup$
    – harpalss
    Jul 22, 2012 at 12:48
  • $\begingroup$ I meant in 3D space, although, now that you mention it, it would also be interesting to consider mass instead. $\endgroup$ Jul 22, 2012 at 13:00

2 Answers 2


Protein interactions occur mostly (if not all) through residues that are on the "surface" and exposed to the milieu in which they exist, be it cytoplasmic or extracellular. So, a naive thought would be to guess that a greater surface area means a greater swathe of exposed regions and probable interacting parts. One protein can bind many others, even simultaneously, through different such interaction surfaces. However, other factors also determine whether a given set of two proteins interact, most important being where they localize in a given cell. If one protein is nuclear but the other on the plasma membrane, it is highly unlikely that they ever interact even if thermodynamics highly favors complex formation. Interaction between two proteins also depends on their respective conformations, which can further be regulated by events such as post translational modifications (eg., phosphorylation by a kinase), bound nucleotide state (eg., GTP vs GDP in a G protein). Last, scaffolds can also sequester and organize protein clusters together spatially and increase the probability of them interacting. All put together, I think it is highly unlikely that just looking at 3D surface area of a protein will say much about its "interactability" with other proteins.


@gkadam is correct and quite exhaustive. There are a lot of things that can affect protein binding, and many of them have little to do with the protein itself, but instead where it is and what else it is doing.

All other things being equal, smaller proteins will form networks more quickly than larger ones for kinetic reasons.

Size differences don't affect how likely two proteins are to interact by itself. Big proteins and little ones interact all the time.

  • $\begingroup$ Sir what are the things that effect protein binding? Is there an exhaustive list of it?? $\endgroup$
    – girl101
    Apr 23, 2015 at 3:51
  • 1
    $\begingroup$ If there is it would be a medium size textbook. pH, temperature, saltiness, conformational changes, adaptor molecules, and the identity of the proteins are the big contributors, but there are many many more. $\endgroup$
    – Resonating
    Apr 23, 2015 at 4:22

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