<p>I am planning to dock a protein to <a href="https://www.selleckchem.com/screening/Flavonoid-Compound-Library.html" rel="nofollow noreferrer">Selleck Chem's Flavonoid Library</a>. I have designed two workflows using Autodock Vina and Schrodinger as follows:</p>
<p><strong>Schrodinger</strong></p>
<ul>
<li>Use their proprietary tools for protein preparation followed by grid preparation under default settings.</li>
<li>Run <code>LigPrep</code> on the SelleckChem library to generate one ligand (at most) per compound under default settings.
<ul>
<li>I executed another run (let's call it 'special run'; see below) generating eight ligands (at most) per compound under default settings.</li>
</ul>
</li>
<li>Run Glide in SP mode under default settings + add a reward for H-bonds.</li>
</ul>
<p><strong>Autodock Vina</strong></p>
<ul>
<li>Run every module of UCSF Chimera's <a href="https://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/dockprep/dockprep.html" rel="nofollow noreferrer">Dock Prep</a> on the Protein under default settings.
<ul>
<li>Except use Reduce in place of AddH - <a href="https://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/addh/addh.html" rel="nofollow noreferrer">suggested</a> by Chimera as a better alternative.</li>
</ul>
</li>
<li>Calculate grid-center to be the centroid of the default ligand and use the same grid size as used in Schrodinger workflow.</li>
<li>Run <code>prepare_receptor4.py</code> but in non-default settings to only remove lone pairs and non-standard residues.
<ul>
<li>We do not remove waters or add charges, as done under default settings; they have been already executed by Chimera.</li>
</ul>
</li>
<li>Download 3D files of each compound in the Selleckchem library from Pubchem in <code>sdf</code> format.
<ul>
<li>Use Obabel to convert them to <code>pdb</code> format.</li>
<li>Run <code>prepare_ligand4.py</code> under default settings to get output in <code>pdbqt</code> format.</li>
<li>Use Obabel to replace Gasteigger charges with <code>eem2015ba</code>.</li>
<li>Use Obabel to minimize energy using <code>MMFF94</code> forcefield under default settings.</li>
</ul>
</li>
<li>Run Vina 1.2 to dock at <code>exhaustiveness</code> of <code>32</code>.</li>
</ul>
<p>The results from the two workflows exhibit <strong>vast disparity</strong> with the correlation coefficient of the rank being about <code>0.2</code>. For example, the best result of Schrodinger is ranked 150 by Vina (the library has about 200 molecules in total) and so on. If I take the best 20 results from Vina and Schrodinger each, there is a single common compound.</p>
<p>In my 'special run', I saw that Schrodinger assigns vastly different overall docking scores to various conformations of the same ligand. This might answer the above disparity unless I am doing something acutely wrong. <em>But</em> that raises the question about how to choose the initial conformation of the ligand if I am constrained to use open-source software and starting conformations influence the final result so severely?</p>

CC BY-SA 4.0
2022-05-24T04:00:38.347Z
Please show the first few lines of results, or whatever other appropriate way can demonstrate this desparity.
gringer
CC BY-SA 4.0
2022-05-24T15:22:17.587Z
@gringer I have added a couple of lines. Does this suffice?
AvadaMouse
CC BY-SA 4.0
2022-05-24T20:14:53.613Z
Yes, thanks. I think that's enough.
gringer
<docking>
How to explain disparities in Flavonoid Docking results between Vina and Schrodinger?
# How to explain disparities in Flavonoid Docking results between Vina and Schrodinger?

(Asked by: username_0 on 2022-05-23)

I am planning to dock a protein to [Selleck Chem's Flavonoid Library](https://www.selleckchem.com/screening/Flavonoid-Compound-Library.html). I have designed two workflows using Autodock Vina and Schrodinger as follows:

**Schrodinger**

* Use their proprietary tools for protein preparation followed by grid preparation under default settings.
* Run `LigPrep` on the SelleckChem library to generate one ligand (at most) per compound under default settings.
  + I executed another run (let's call it 'special run'; see below) generating eight ligands (at most) per compound under default settings.
* Run Glide in SP mode under default settings + add a reward for H-bonds.

**Autodock Vina**

* Run every module of UCSF Chimera's [Dock Prep](https://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/dockprep/dockprep.html) on the Protein under default settings.
  + Except use Reduce in place of AddH - [suggested](https://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/addh/addh.html) by Chimera as a better alternative.
* Calculate grid-center to be the centroid of the default ligand and use the same grid size as used in Schrodinger workflow.
* Run `prepare_receptor4.py` but in non-default settings to only remove lone pairs and non-standard residues.
  + We do not remove waters or add charges, as done under default settings; they have been already executed by Chimera.
* Download 3D files of each compound in the Selleckchem library from Pubchem in `sdf` format.
  + Use Obabel to convert them to `pdb` format.
  + Run `prepare_ligand4.py` under default settings to get output in `pdbqt` format.
  + Use Obabel to replace Gasteigger charges with `eem2015ba`.
  + Use Obabel to minimize energy using `MMFF94` forcefield under default settings.
* Run Vina 1.2 to dock at `exhaustiveness` of `32`.

The results from the two workflows exhibit **vast disparity** with the correlation coefficient of the rank being about `0.2`. For example, the best result of Schrodinger is ranked 150 by Vina (the library has about 200 molecules in total) and so on. If I take the best 20 results from Vina and Schrodinger each, there is a single common compound.

In my 'special run', I saw that Schrodinger assigns vastly different overall docking scores to various conformations of the same ligand. This might answer the above disparity unless I am doing something acutely wrong. *But* that raises the question about how to choose the initial conformation of the ligand if I am constrained to use open-source software and starting conformations influence the final result so severely?

**Tags:** docking
> **Comments:**
> **username_1**: Please show the first few lines of results, or whatever other appropriate way can demonstrate this desparity.  
> **username_0**: @gringer I have added a couple of lines. Does this suffice?  
> **username_1**: Yes, thanks. I think that's enough.  

---

## 0 answers

