Small Molecule Superposition Tool

Question

[Nir London]

Hi Everyone,

Does anyone knows of a good tool for the super-positioning of small molecules? Preferably from command-line/scriptable. The task it should solve e.g. is given one conformation for a small molecule, compare it to a large database of conformations and calculate RMSD. Optimally the molecules shouldn't even be identical or in the same frame of reference.

Your input is most appreciated!

[dimkal]

can you clarify, when you say "databse of conformations" do you mean same molecule or all different molecule.

Answer 1

[Egon Willighagen]

The Chemistry Development Kit can do this. It has a few algorithms for MCS to determine how two molecules should be aligned, as well as a RMSD-based algorithm to align two molecules via the shared MCS. This functionality is used in Bioclipse, and can be scripted as detailed in this blog post, and reproduced here:

var smileses = new Array("CC(C)C", "CCCN", "CCC=O");

var unaligned = cdk.createMoleculeList();
for (i=0; i<smileses.length; i++) {
  mol = cdk.fromSMILES(smileses[i]);
  mol = cdk.generate3dCoordinates(mol)
  unaligned.add(mol);
}

var aligned = cdk.kabsch(unaligned)

jmol.load(aligned.get(0));
for (i=1; i<aligned.size(); i++) {
  jmol.append(aligned.get(i));
}

The last code bit visualized the alignment in Jmol.

Since you are looking at conformers, it may be possible to take advantage of the fact that atom ordering is identical, allowing you to skip the MCS step, but that is harder to do with the current Bioclipse APIs.

Answer 2

[Flow]

I would recommend you chemaxon tools or also open eyes tools

[Nir London]

Do you know of a specific tool or API command? or generally assume they have one?

[Flow]

I was in several conferences and they were always there talking about their products for this purpose. Can not remember details. I encorauge you to visit their websites, good luck!

[Flow]

Chemaxon tools are free btw!

Answer 3

[Alastair Kerr]

The structural labs here use Lidaeus

LIDAEUS (LIgand Discovery At Edinburgh UniverSity) is a high throughput in-silicon screening program written by Dr Paul Taylor of the Institute of Structural and Molecular Biology, University of Edinburgh. LIDAEUS is a highly adaptable and modular rigid body docking in-silicon screening code written in C++. [?]

Answer 4

[Woa]

FlexS (commercial, scriptable)

Answer 5

[dimkal]

I'm know that Schrodinger has such tools like substructure search and small molecule fingerprints. Small molecule matching is not a trivial thing, and in my opinion Schrodinger tools do the best, not free though.

Answer 6

[mikmaksi]

I'll recommend Visual Molecular Dynamics, since no one has mentioned it yet. It's definitely command-line scriptable.

[dimkal]

vmd cannot automatically alight a ligand. You need to specify corresponding atoms to VMD. also it's not trivial to align ligands with different chemistry