Constrained minimization of docked ligand

[Xu Youjun]

Hi,
I would like to implement a contrained score after the "--minimized". It just means, some part atom positions are fixed in the minimized process. I read the source code of smina, and found the branch tree would be parsed by the ligand OBmol. So I tried to keep the root position not be updated in each step of bfgs. I just understand this root position with p vector (see the following code ) could move the whole ligand positions. Thus I assign zero to them. But the orientations and torsions are allowable. Am I right? Any suggestions for implementing the function? Thx

bfgs.h:L130

    p(0)=0;
    p(1)=0;
    p(2)=0;
    for (;;) //always try full newton step first
    {
        x_new = x;
        x_new.increment(p, alpha);
        f1 = f(x_new, g_new);

Best regards,
YJ

[David Koes]

You don't need to modify the source code. Provide the ligand as the "flex" argument as a pdbqt that is formatted so the ROOT is the part you don't want to move.

[David Koes]

You'll need to pass the --no_lig argument as well so smina knows there is no ligand and it should just optimize the flex part.

[Xu Youjun]

I tried the follow command,

smina -r examples/protein.pdbqt --flex examples/ligand0009695.pdbqt --autobox_ligand demo.sdf --no_lig --minimize -o examples/out_lig.pdbqt

But the parse_error called "Parse error on line 15 in file "examples/ligand0009695.pdbqt": Unknown or inappropriate tag". here in the file is a tag "ROOT"

I guess I may should place the root part of the ligand into the Rigid part in the create_init_model?

[Xu Youjun]

May I have to refer to an example file as --flex argument?

[David Koes]

Each separate component needs to be wrapped in BEGIN_RES/END_RES as is output, for example, with the -xs option for openbabel pdbqt export:

BEGIN_RES ASP X 613
ROOT
ATOM      1  C   ASP X 613      46.673  49.691  53.077  0.00  0.00    +0.000 C 
ENDROOT
BRANCH   1   2
ATOM      2  C   ASP X 613      45.842  49.784  54.303  0.00  0.00    +0.000 C 
ATOM      3  O   ASP X 613      46.347  49.741  55.471  0.00  0.00    +0.000 OA
ATOM      4  O   ASP X 613      44.635  49.793  54.100  0.00  0.00    +0.000 OA
ENDBRANCH   1   2
BRANCH   1   5
ATOM      5  C   ASP X 613      45.963  50.454  51.954  0.00  0.00    +0.000 C 
ATOM      6  C   ASP X 613      46.371  51.957  51.944  0.00  0.00    +0.000 C 
ENDBRANCH   1   5
END_RES ASP X 613