Hello and many thanks for supporting this amazing tool!
The problem: upon installation, my Build menu is different from what the online manual describes. Specifically, Build–>Insert has Molecule; DNA/RNA; InChl and SMILES options, but no peptide builder option.
Environment Information
Avogadro version: 1.99.0
Operating system and version: Windows 10 Enterprise, version 22H2
Just one more question, please. Imagine I do have the peptide builder working within Avogadro, either by using the Python script or by waiting until you have implemented it in Avogadro2. Will I then be able to use Build or Draw to place a proton on a residue and then use the geometry optimization to find the optimal geometry of the molecular ion within a force field that would recognize the proton as a proton and not as a neutral hydrogen? This was my actual goal…
When adding atoms Avogadro doesn’t distinguish between charges or oxidation states so you would just add a normal hydrogen. By default the “Adjust Hydrogens” feature is on, and this prevents you from adding extra hydrogens, so make sure to turn it off first (in the Draw Pane, visible on the left when you select the Draw Tool).
Currently however, while Avogadro does do valence-based calculations, the formal charges aren’t adjusted automatically. So to make sure it is being treated as a protonation you’ll have to manually change the formal charge (of the nitrogen you’re protonating) to +1 in the Atom Properties dialog (Analysis => Properties => Atom Properties...). Then the formal charge will be stored by the program, saved in CJSON files, and reflected in the calculation of the overall charge.
Whether the overall charge of the molecule or the formal charges of the atoms is used within the force field optimizations I don’t know, and Geoff will have to answer that.
I can tell you though that geometry optimizations using my avo_xtb plugin definitely support charged molecules, so there’s always that option.
It depends very much on the force field. Normally some adjustment is made for formal charges, but having say a protonated histidine doesn’t mean the \ce{H+} is really a “proton” for most force fields.
There’s been some discussion about balancing “I want to specify the formal charge when editing” and ease of use. I’m open to suggestions, but I’m generally more in favor of methods like XTB, etc. that don’t require formal charges or atom typing. In reality, there’s never really an \ce{H+}
I have followed Matterhorn’s advice and, taking an amino acid as a trial molecule, put a couple of “protons” on it by adding hydrogens and changing the formal charge of the corresponding nitrogens. The energies and the optimised geometries that I obtained this way looked a bit strange, so I checked the partial charges table and “discovered” that these partial charges sum up to zero, regardless of my protonation effort… Is it an Avogadro or an MMFF94 feature or am I still doing something wrong?
It would actually be very nice to have this working, as I finally realised that Avogadro2 has the standard amino acids in Insert–> Molecule, so combining them into a short peptide, such as I would be interested in, is not very tedious even without a proper peptide builder.
I will, of course, try to add the XTB extension (thanks, Matterhorn!).
Many partial charge methods (e.g., Gasteiger) do not properly account for formal charges that sum to an ion. I’ve never quite understood why, but that’s always been my incentive to use semiempirical quantum calculations like MOPAC or xtb.
I am convinced I should use xtb or similar, but I cannot follow the instructions for installing the xtb plugin by Matt… Probably I should start a new thread since it has nothing to do with the peptide builder I was after initially.
