<p>I am an undergraduate novice, from CS major, intending to run a virtual-screening run using Autodock Vina. A few questions in this regard:</p>
<ul>
<li><p>How to choose the best charge model for the ligand?</p>
<ul>
<li><a href="https://pubs.acs.org/doi/suppl/10.1021/acs.jcim.1c00203/suppl_file/ci1c00203_si_001.pdf" rel="nofollow noreferrer">By default</a> (p. 2), Vina installs Gasteiger-Marsili (GM) partial charges prior to docking. However, GM, being a conformationally-independent approach, is a poor choice when <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667495/" rel="nofollow noreferrer">compared</a> to other conformationally-dependent approaches.</li>
<li>In that case, can I choose <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667495/" rel="nofollow noreferrer">B3LYP/6-311G/AIM</a> which is the best-performing EEM-parametrization-set, yet published?
<ul>
<li>What are the upsides and downsides?</li>
</ul>
</li>
</ul>
</li>
<li><p>How to choose the best charge model for the protein?</p>
<ul>
<li>Once again, Vina installs Gasteiger-Marsili (GM) partial charges prior to docking and there <a href="https://jcheminf.biomedcentral.com/articles/10.1186/1758-2946-1-15" rel="nofollow noreferrer">exist</a> better models.</li>
<li>Is there any better open-source alternative than <a href="http://openmopac.net/" rel="nofollow noreferrer">MOPAC-PM7</a>?</li>
</ul>
</li>
<li><p>Vina removes non-polar hydrogens and lone pairs from the ligand as well as protein.</p>
<ul>
<li>Is there any upside to this operation other than <a href="https://www.scripps.edu/sanner/python/adt/Tutorial/AutotorsTutorial.html" rel="nofollow noreferrer">decreasing computational complexity</a>?</li>
<li>If time etc. is not a factor, are docking outputs going to be affected to any significant degree in absence of this modification?</li>
</ul>
</li>
</ul>

CC BY-SA 4.0
2022-03-28T07:22:12.120Z
@M__ Narrowed down [my previous question](https://bioinformatics.stackexchange.com/questions/18837/choices-for-a-docking-run)
AvadaMouse
CC BY-SA 4.0
2022-03-28T08:55:31.317Z
Ideally StackExchange questions should be related to a single problem. Can you please give more details about your project / problem? If this is for an assignment (or similar canned problem), please add the tag 'homework'. If you're interested in general discussion rather than a solution to a specific problem, I recommend you instead post to https://reddit.com/r/bioinformatics
gringer
CC BY-SA 4.0
2022-03-28T10:42:26.663Z
Your opening statement forces me to ask: have you done a re-docking test with vanilla settings and what was wrong with it? Or are you well past that step?
Gasteiger partial charges are more than adequate. The drude particle mod in some FF addresses the polarisability problem, but is uncommon. Some people run QM charge calculations in Gaussian, for better partial charges, but most folk don't. The major issues in docking stem from protein —charged active site sidechains, especially involving cysteine and histidine, loops that ought to have been flipped to close up on the complex etc
Matteo Ferla
<docking>
Ligand and protein preparation in Vina docking
# Ligand and protein preparation in Vina docking

(Asked by: username_0 on 2022-03-28)

I am an undergraduate novice, from CS major, intending to run a virtual-screening run using Autodock Vina. A few questions in this regard:

* How to choose the best charge model for the ligand?

  + [By default](https://pubs.acs.org/doi/suppl/10.1021/acs.jcim.1c00203/suppl_file/ci1c00203_si_001.pdf) (p. 2), Vina installs Gasteiger-Marsili (GM) partial charges prior to docking. However, GM, being a conformationally-independent approach, is a poor choice when [compared](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667495/) to other conformationally-dependent approaches.
  + In that case, can I choose [B3LYP/6-311G/AIM](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667495/) which is the best-performing EEM-parametrization-set, yet published?
    - What are the upsides and downsides?
* How to choose the best charge model for the protein?

  + Once again, Vina installs Gasteiger-Marsili (GM) partial charges prior to docking and there [exist](https://jcheminf.biomedcentral.com/articles/10.1186/1758-2946-1-15) better models.
  + Is there any better open-source alternative than [MOPAC-PM7](http://openmopac.net/)?
* Vina removes non-polar hydrogens and lone pairs from the ligand as well as protein.

  + Is there any upside to this operation other than [decreasing computational complexity](https://www.scripps.edu/sanner/python/adt/Tutorial/AutotorsTutorial.html)?
  + If time etc. is not a factor, are docking outputs going to be affected to any significant degree in absence of this modification?

**Tags:** docking
> **Comments:**
> **username_0**: @M__ Narrowed down [my previous question](https://bioinformatics.stackexchange.com/questions/18837/choices-for-a-docking-run)  
> **username_1**: Ideally StackExchange questions should be related to a single problem. Can you please give more details about your project / problem? If this is for an assignment (or similar canned problem), please add the tag 'homework'. If you're interested in general discussion rather than a solution to a specific problem, I recommend you instead post to https://reddit.com/r/bioinformatics  
> **username_2**: Your opening statement forces me to ask: have you done a re-docking test with vanilla settings and what was wrong with it? Or are you well past that step? Gasteiger partial charges are more than adequate. The drude particle mod in some FF addresses the polarisability problem, but is uncommon. Some people run QM charge calculations in Gaussian, for better partial charges, but most folk don't. The major issues in docking stem from protein —charged active site sidechains, especially involving cysteine and histidine, loops that ought to have been flipped to close up on the complex etc  

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## 0 answers

