text: user388: Can anyone recommend a protocol for building the 3D structure of a small molecule de novo, given only a 2D rendering? So far my idea has been to build the molecule using the fragment builder in PyMol, then make conformers using Frog2. But I have no idea how realistic the starting structure is from PyMol and how exhaustively the conformers are sampled in Frog2.
  The downstream application of this would be to dock the ligand into a protein binding pocket. If anyone has a more rigorous protocol for making sure all the conformational space is fully sampled, it would be greatly appreciated!
  
  user6322: Most universities have a ChemDraw site lincence, so you may want to check that for drawing a non–3D-embedded molecule. Alternatively there are many other programs. PyMOL is not really a good choice. Also there are online drawing tools everywhere, where you can download a SMILES (see below).
  Chemical formula is the wrong way to go, unless you are "enumerating".
  The chemical formula of glucose is C6H12O6. This is the same for all hexoses. What you want is a SMILES. This string gives the connectivity of the atoms. For D-glucose it's OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O, the @ symbols are chiral centres.
  In Cheminformatics making a list of all possible compound with n-carbons is a big deal, this is called enumeration and you likely don't have to reinvent wheel. Furthermore, there are datasets that are filtered by the Lipinski rule.
  
  GDB datasets (if you don't care if you cannot buy it)
  Zinc-DB  (if you care if you can buy it)
  Enamine Real (if you care if you can buy it reasonably)
  
  
original_text: 388: <p>Can anyone recommend a protocol for building the 3D structure of a small molecule <em>de novo</em>, given only a 2D rendering? So far my idea has been to build the molecule using the fragment builder in PyMol, then make conformers using Frog2. But I have no idea how realistic the starting structure is from PyMol and how exhaustively the conformers are sampled in Frog2.</p>
  <p>The downstream application of this would be to dock the ligand into a protein binding pocket. If anyone has a more rigorous protocol for making sure all the conformational space is fully sampled, it would be greatly appreciated!</p>
   6322: <p>Most universities have a ChemDraw site lincence, so you may want to check that for drawing a non–3D-embedded molecule. Alternatively there are many other programs. PyMOL is not really a good choice. Also there are online drawing tools everywhere, where you can download a SMILES (see below).</p>
  <p>Chemical formula is the wrong way to go, unless you are &quot;enumerating&quot;.
  The chemical formula of glucose is <code>C6H12O6</code>. This is the same for all hexoses. What you want is a SMILES. This string gives the connectivity of the atoms. For D-glucose it's <code>OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O</code>, the <code>@</code> symbols are chiral centres.
  In Cheminformatics making a list of all possible compound with n-carbons is a big deal, this is called enumeration and you likely don't have to reinvent wheel. Furthermore, there are datasets that are filtered by the Lipinski rule.</p>
  <ul>
  <li><a href="https://gdb.unibe.ch/downloads/" rel="nofollow noreferrer">GDB datasets</a> (if you don't care if you cannot buy it)</li>
  <li><a href="https://zinc.docking.org/" rel="nofollow noreferrer">Zinc-DB</a>  (if you care if you can buy it)</li>
  <li><a href="https://enamine.net/library-synthesis/real-compounds/real-database" rel="nofollow noreferrer">Enamine Real</a> (if you care if you can buy it reasonably)</li>
  </ul>
  