Docking Metal Ions to Enzymes to Assess Potential Inhibitory Interactions

[n-vivek]

Hi,
I’m exploring the possibility of using AutoDock Vina to assess the potential inhibitory activity of metal ions such as Ag+, Mn2+, Hg2+, etc.. on specific enzymes. My aim is to dock these ions to the protein and analyze whether they interact with catalytically important residues, potentially disrupting the enzyme’s function.

While there are several online tools that predict metal-binding and interacting residues in proteins, I believe docking can provide more definitive insights into actual binding interactions and their possible inhibitory effect.

I would like to ask:

1. Does AutoDock Vina support docking of metal ions like Ag+, Mn2+, Hg2+, etc.?
2. If so, are there any specific considerations or best practices for setting up such a docking experiment (e.g., charge handling, force field parameters)?
3. Can Vina meaningfully estimate binding poses and interactions for such small ions with protein residues?

Any guidance or references would be greatly appreciated.

Thanks & regards,
Vivek.

[diogomart]

Hello,

1. Yes.
2. I don't think this has been tested. There's two scoring functions in Vina (the program), the AD4 scoring function, and the Vina scoring function. Not all metals are supported. AD4 scoring is more similar to a classical force field with vdW and electrostatics, while Vina treats all metals the same (yes they are indistinguishable) and does not use electrostatics. In Vina scoring function, a metal is just a H-bond donor species.
3. I would guess not, but could generate starting poses for molecular dynamics (MD) simulations.

[n-vivek]

Thank you so much for the clarification @diogomart .

I’ll try generating poses using Vina as a rough starting point, and will also explore docking using the AD4 scoring function, which seems more suitable for my use case.

Appreciate the insights. I’ll follow up if I run into anything interesting or unexpected during the process.

Thanks again!