Member Site Forums Rosetta 3 Rosetta 3 – General Modeling phosphate ion binding site in protein. Reply To: Modeling phosphate ion binding site in protein.


    Certainly if you’re attempting to design a phosphate binding site, Rosetta not being parametrized well on phosphate binding sites might be a limitation, as it may mispredict interactions. However, for designing a binding site from scratch, you’re probably more limited by the number of interactions you can make to the phosphate. Native phosphate binding sites tend to have numerous interactions to the phosphate, and it’s currently difficult for Rosetta to put in all of the interactions, due to geometry limitations.

    If you already know where the phosphate will bind, your better bet is to use the “catalytic constraints” facility of enzyme design. That is, put in the phosphate binding interactions/geometry with an enzdes constraint file. If you do it this way, Rosetta will keep those interactions (somewhat) fixed, and then will spend its time optimizing the other interactions to the protein (e.g. the other molecules/moieties you’re putting in with your design).

    By the way, it might help to give a broad overview of the general task you’re trying to accomplish. No guarantees, but we may be able to suggest a different route to the same goal, as opposed to treating each stumbling block du jour one at a time.

    P.S. If you’re doing enzyme design with a phosphate, you may want to add a “hack_elec 0.25” to your weights file. hack_elec is a coulombic electrostatic term, which would likely help with your charged substrate. It’s turned on for ligand docking, but isn’t currently included on in the default enzyme design weights file.