Yes, I do agree that we should have something like nspc said.
I would also like to add on that I think the supposed hypothetical contextual menu should be so that only every oxygen (to accommodate for ether groups), carbon, & nitrogen (to accommodate for tertiary amine groups/quaternary ammonium cation groups [e.g. acetylcholine - an important physiological ligand in the nervous system containing both quaternary ammonium cation & ether functional groups]) atom has its own set of viable functional group options. This means that when designing ligands, I think it should be so that every carbon, oxygen, and nitrogen atom is its own molecule part.
I think that how this hypothetical contextual menu would supposedly work is so that, since each and everyone of those atoms can make their own number of bonds, so there should be a list of available options for each bond.
I think that this also means that there should also be a way to select exactly which bond on that atom to be modified, so each bond of the atom should be indexed, and respectively and –distinctively, including but not limited to towards color-blind people–, highlighted in the 3D rendering of the atom itself in the ligand.
Because of the large number of functional groups and chemicals and known organic reactions (e.g. hydroxylation, haloalkanes, hydroxylamine, Rosenmund-von Braun synthesis, Kolbe nitrile synthesis) in organic chemistry, this will open up a larger number of possibilities and combinations for Foldit players to recognize and memorize and compare.
For example, I think Foldit players should be able to replace white hydrogen atoms with purple atoms.
This is called hydroxylation, which is replacing a hydrogen atom in a C-H bond with a O-H (hydroxyl group, the top of serine), physiologically usually via iron compounds as a catalyst in the enzyme cytochrome P-450. For more, please see https://en.wikipedia.org/wiki/Hydroxylation .
I also think Foldit players should be able to replace white hydrogen atoms with green atoms.
This can be done via Free-radical halogenation, which is replacing a hydrogen in a C-H bond with a halogen atom via a diatomic halogen molecule. For more, please see https://en.wikipedia.org/wiki/Free-radical_halogenation .
I also think Foldit players should be able to replace a green atom in a Carbon-Green atom bond with a carbon atom triple bonded to a blue atom (nitrile group).
This can be done via nucleophilic substitution. For more, please see https://en.wikipedia.org/wiki/Nucleophilic_substitution .
Also, Foldit players should be able to replace the nitrile group in a Carbon-Nitrile bond with either:
- a carbon connected to two red atoms (carboxylic group - the top of glutamate), via "hydrolysis under reflux with mineral acid catalyst, or"
- a carbon single-bonded to a blue atom (amine group - the top of lysine), via "reflux under dry ether, followed by addition to H20"
For more about the possible reactions with Nitrile groups, please see https://en.wikipedia.org/wiki/Nitrile#Reactions .
There are many more chemicals and chemical reactions that involve organic compounds in organic chemistry, so the premise of having the limited options as provided in the Reaction Design tool as of now for designing a ligand that can bind to a receptor is not, even intuitively, efficient nor creative in the long-term. I think we are not looking at more efficient and strategic ways to do things like this.
I think this contextual menu would be helpful in designing ligands because it would allow for the strategy to make small atom-by-atom modifications on the ligand and then wiggling, which stimulates the process of natural selection/evolution, like mutations in DNA. Also, it would be helpful in terms of diversity and creativity in the designed ligands.
In this feedback would also like to take into consideration and respond to the premise that "the last thing we want is to create a wonderfully scoring small molecule that wouldn’t be possible in the real world, or worse would explode!". If that is the case, the preventative measures that should be taken would be to make a referenceable list of all the criteria that should be met for the ligands, and what can and can not be allowed. It is just like coding.
You have to outline all of the possibilities and things for AI to truly develop an efficient and outstanding way in developing solutions to problems.
- Another thing I want to point out for the developers and scientists to consider that fits with this feedback in general is the possibility of having the feature of calculating the energy & compounds needed (chemicals that are only needed to make this particular ligand) & cost(as in money) and scientific equipment (e.g. enzymes, yeast cells, centrifuge, etc.) needed to add these functional groups to the ligand in this supposed contextual menu, and displaying it to the Foldit players and possibly adding any criteria (e.g. cost limit, energy limit, equipment not allowed, etc.).
I believe the consideration of the situation that would occur on the scientist's side of the table would increase the efficiency and productivity of the Foldit players, because the more goals they have to reach, the more motivated they are. I also believe that the premise of having optional requirements of utilizing certain chemical reactions that can be conducted with certain scientific equipment can be energy-efficient. Plus, with these requirements, the planning will already be half-done to make this compound. Feel free to modify this idea to fit your specialties as needed.
Thank you for reading through my thoughts on nspc's idea!
From, donuts554.
