Automatic Analysis Of Molecular Flexibility

Question

[Flow]

We want to test some enhanced scoring function in docking of flexible ligands. Our main bootleneck is the automatic analysis of ligand flexibility, i.e., which parts or fragments of the molecule to consider rigid and which not, for example, in terms of flexible dihedral angles. We wonder if there are open source libraries (not another programs) which we could use for such purpose.

PS: I got information that there is a possibility to do this with Chemistry Development Kit (Egon Willighagen)

PS2: Another option seems to be OpenBabel since it can detect rotatable bonds

Answer 1

[Egon Willighagen]

Yes, the Chemistry Development Kit can do that. Just as an example, there is a Rotatable Bond Count descriptor implemented.

There are various approaches you can take, and it depends a bit on what you qualify something as a rigid bond. We have functionality to

• identify ring bonds (SpanningTree class)
• detect double/triple bonds (simple iteration over all bonds)
• detect ring systems (we have at least three algorithms to find ring systems)
• classes to do fragmentation, such as the Murcko approach

Answer 2

[Vladimir Chupakhin]

Flexible ligand docking is for now de facto parameter for docking. So you can use any of the docking software: AutoDock/AutoDock Vina for example.

[Flow]

I said library not another program

[Flow]

sorry for the confusion, I have updated the question

[Hans Laxness]

anyway, could autodock do that?

[Vladimir Chupakhin]

in term of library - try OpenEye Omega

[Vladimir Chupakhin]

and yes, autodock can do that

[Flow]

OpenEye Omega can only generate conformers, but I do not see information related to fragment/flexibility analysis

[Vladimir Chupakhin]

Sorry, I don't understand. There is bond - it can be aromatic thou not flexible. All others are mostly flexible even in the rings. OpenEye Tools can clearly state which bond is flexible and which are not.