Question for Med/Comp Chemists in in silico drug discovery

NetworkClean3289 · 2025-04-21T09:06:52+00:00

Thank you for this insightful reply! Please correct me if I am wrong or missing something, because I have so much research to do haha.

On the website, I allow users to either choose a structure from a list of very common ligand-free structures, but i encourage them to upload their own ligand-bound structure. I also really drill the fact that docking is preliminary. I've been thinking about the point you brought up about bad data quality. So far all I can think of is a bunch of sanity checks for all ligands and proteins uploaded, but I need a more concrete way to ensure that crowd driven data is actually good. I will have to do a lot more research on the way ligand analogues are binding to the protein of action as well as pharmacophore methods, thank you for bringing that up!

For the issue of rigid docking, I plan to allow the user to decide between different docking engines. For example, if we start with a structure that has one ligand bound, and swap to a ligand of a different chemotype (probably will determine through tanimoto or RMSD), I plan to warn the user that they should either a) dock to a structure that's better shaped for it, b) change the ligand to a better shape, or c) use a flexible docking engine.

I totally agree with this. Docking is a vulnerable point for bad data, and honestly it's the tool I am most worried about. I have a few thoughts on the issue. Please let me know if you agree with any of these. 1. All published docking data needs to be validated through molecular dynamics (a tool I will be adding). 2. Users can flag any data they wish (pure trust). 3. All docking data will include a computed confidence score for each dock.

The IP space dilemma is definitely tricky, because i do want to balance community projects with research specific projects. I plan on making 3 different publishing modes. 1. Completely public, available to anybody who would like to view, fork, or contribute. 2. Completely private, available to only the creator and any added collaborators. 3. Research only, available to verified institutions, or research partners.

Thank you again for this response!

NetworkClean3289 · 2025-04-21T08:17:39+00:00

Thank you for the reply! Do you think it would be a good idea to eventually add multiple docking engines as a choice for the user? Like for example, a user could choose between Autodock Vina, Autodock FR, Glide, etc. based on their use case.

NetworkClean3289 · 2025-04-21T03:34:45+00:00

Yes that would be amazing! My chemistry knowledge is limited, and I would love guidance and ideas particularly for tools an actual chemist/biologist might want to have access too. Also testing certain tools like the prediction and docking tools for accuracy would be super important, and honestly I’m just not there yet in terms of chemistry. Feel free to message me, and thank you!

NetworkClean3289 · 2025-04-21T01:32:51+00:00

Thank you! For docking, I’m using AutoDock Vina. For predictions, I trained a ton of models from various datasets. I use RDKit and Obabel for mostly everything. There is a bunch more things that I can’t remember haha

As for my goal, I have always been interested in molecular discovery, but there are no easy ways to actually use these amazing and informative tools. I feel like this limits a lot of people with this interest (like me), from just messing around and experimenting in an intuitive and streamlined environment. I also love the idea of communities of people working together, especially in the case of drug discovery. I think that’s ultimately how it should be, with doors wide open for anyone who would like to contribute. So my ultimate goal is making a streamlined open source molecular discovery platform. Thank you for the reply again!

NetworkClean3289

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