Small Molecule Design Tool

The highly anticipated updates to the Small Molecule Design Tool are here, and we have a series of puzzles on the way! Your continued efforts in protein design have been nothing short of remarkable, and we are excited to be able to further help this amazing community contribute to small molecule design. While protein based drugs are an increasingly important category of therapeutics, the majority of drugs continue to be small-molecule based. With the Small Molecule Design tool you will be able to create, edit, and enhance small molecules.

Let's dive in and see how the Small Molecule Design Tool works. The tool will come up as an option in the Selection Mode action bar when you select a designable small molecule on a puzzle which supports it. With the Small Molecule Design Tool open, you can select particular atoms in the designable ligand to act on. The tool has two distinct panels: Atom Selection and Fragment Selection. You can toggle between them with the central Panel Selection Button.

The Atom Selection Panel has two unique areas: The Atom Selection area at the top and the Bond Selection area in the middle. With Atom Selection, selected atoms can be replaced with an atom of your choosing, assuming the placement is allowed. With Bond Selection, you will be able to select two atoms, and change the bond type between them.

The Fragment Selection Panel works with groups of atoms. The category buttons in the middle organize the fragments into four separate groups: Functional Groups, Unsaturated Cyclic, Saturated Cyclic, and Polycyclic. Each choice will change the contents of the Fragment Selection area above. Once you’ve selected the type of fragment, you can select the location (the atoms) on the small molecule where you want it to go, and then select which fragment you want from the Fragment Selection area. This will pop up a sub-panel which allows you to select where on the fragment you want to place the attachment. Using the `A`, `S` and `TAB` keys while hovering over the selection in the subpanel will allow you to further customize how the fragment is placed.

You may have noticed that both panels share a couple of elements. These are the Panel Selection Button, which allows you to switch between the Atom Selection Panel and the Fragment Selection Panel, and the Cleanup Structure area, with which you can delete atoms, delete bonds, and deselect highlighted atoms.

Be sure to check out the new tutorials to help get you started! We can't wait to see what all you come up with. Happy building!

( Posted by  Sciren 46 128  |  Tue, 10/12/2021 - 21:45  |  4 comments )
cas0362's picture
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Joined: 08/15/2017
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Fun with fragments not working ?

The fun with fragments tutorial does not appear to be working at the moment. It has a red outline.

Sciren's picture
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Joined: 06/29/2019
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Fun with Fragments tutorial

Hi cas0362! I'm sorry you are experiencing an issue with the Fun with Fragments tutorial. If I could, I would like to get some more information on what you are seeing. Have you completed the Inside the Pocket tutorial? Fun with Fragments is only accessible once you have completed the previous tutorial. If you haven't, it is by design that you would see a red outline with an inactive/darker image, and be unable to play the tutorial.

alcor29's picture
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Joined: 11/16/2012
Questions re 2062

1. I looked at the 'small molecule color' and unfortunately selected one by mistake. Now can't go back to ligand color ochre n View Menu. Please include this color as a choice so we don't have to reboot (some of the colors available there have probs, i.e white blends in with protein, yellow too close to S, etc.

2.What is a MMF wiggle?
3.Why do we see red balls with skinny bonds? What do they mean? Are the Oxygens? Acceptors?

rmoretti's picture
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Joined: 01/15/2010
Groups: Foldit Staff
2. MMFF wiggle is a wiggle

2. MMFF wiggle is a wiggle which uses the "Merk Molecular Force Field", a small-molecule based scoring method, rather than the standard Foldit/Rosetta scoring method. We include it because it may help in some situations. It might not, though, and since it's using a different scoring function from the one used for the top line score, it may make your score go down rather than up. (Think of it a bit like wiggling with a different CI - it's not directly equivalent, as it doesn't change the scoring is exactly the same way CI does, but it's a similar sort of "use an altered score to get different behaviors")

3. I think what you're referring to is the display which comes from "show bondable atoms" option in the view menu. These blue & red balls coming off of the protein cartoon are the actual locations of the nitrogen and oxygen atoms of the protein backbone. They're displaced (on sticks) from the main cartoon backbone representation because the cartoon version is smoothed a bit for a clearer display. The red balls are indeed oxygens which are hydrogen bond acceptors. The blue ones are nitrogens which are hydrogen bond donors.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons