Body: <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>
  
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2022-05-24T04:00:38.347Z
Comments.Text: Please show the first few lines of results, or whatever other appropriate way can demonstrate this desparity.
Comments.UserDisplayName: gringer
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2022-05-24T15:22:17.587Z
Comments.Text: @gringer I have added a couple of lines. Does this suffice?
Comments.UserDisplayName: AvadaMouse
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2022-05-24T20:14:53.613Z
Comments.Text: Yes, thanks. I think that's enough.
Comments.UserDisplayName: gringer
Tags: <docking>
Title: How to explain disparities in Flavonoid Docking results between Vina and Schrodinger?
ThreadText: # 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**: @username_1 I have added a couple of lines. Does this suffice?  
  > **username_1**: Yes, thanks. I think that's enough.  
  
  ---
  
  ## 0 answers
  
  