The question of ligand docking with constraints

[Anonymous]

Hello,

I read the paper Rosetta and the Design of Ligand Binding Sites

and it enlightens me.

According to the method of this paper,  I design my enzyme.

However,  I find these are a few unreasonable results which show reaction atom of ligand  do not close to  catalytic triad,

but  the opposite side of ligand close to  catalytic triad.

So I want to  make docking with  constraints. 

I think it can achieved with ConstraintSetMover, but  do not understand how write the Constraint File.

 

For example,  I want to set the distance betweent  atom CA of  resid 516 (one of catalytic triad)  and C1 of ligand, and the distance is 3 ± 0.5 A .

AtomPair  516 CA   585  C1 HARMONIC  Func_Def 

I  read  the  equation f(x)=[(x-x0)/sd] ^2 , but I do not konw how to set  3 ± 0.5 A in HARMONIC function.

I think ” AtomPair  516 CA   585  C1 HARMONIC  3  0.5 ” is wrong

Could  give a right sample that how  to set distance  (3 ± 0.5 A)?

Thanks~

 

 

[Anonymous]

Since you found the harmonic equation I assume you found the constraints doc page: https://www.rosettacommons.org/docs/latest/rosetta_basics/file_types/constraint-file

You can’t set a “range” of 3 +- 0.5 with harmonic.  It’s a parabola, it doesn’t have a range, it is defined over all possible X.  You can play with the SD parameter such that the parabola is narrower or wider, which will have the effect of disfavoring  / being permissive of distances further from 3 angstrom, but you can’t forbid values outside the 2.5-3.5 range.

Square well functions don’t work terribly well with Rosetta because they are unminimizable, but reading the doc page I do see FADE which may be of some use.  Find FADE on the page and see if meets your needs better?

I always encourage people to plot out constraint energy value vs. x deviation in the plotting software of their choice to get a feel for how strong a constraint they are creating.  Remember that “good residues” are in the range of -3 to -2 energy units.

[Anonymous]

Thanks for your suggestion.

Function of constraint energy is complicated.

I will have a try  ~~

[Anonymous]

If you’re looking to do something like a harmonic function, but have a range (instead of a point) which has a zero value, I’d recommend the FLAT_HARMONIC function.

This will allow you to set a range where the constraint will have no penalty, and then you’ll get a harmonic penalty for any deviation outside that range. Depending on how stringently you set your sd value, you can get something rather close to a “square well” function. (But as mentioned, that’s probably not necessary. You don’t need much of a penalty to keep Rosetta from sampling it.)

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