Great write up, we're working on a drug discovery CAD tool and MD has been one of our focal points. Extremely challenging and fun problem to work on!
What complicates things is the experimental data we get back from labs to validate MD behavior is extremely tricky to work with. Most of what we're working with is NMR data which shows flexibility in areas of the proteins, but even then we're left with these mathematical models to attempt to "make sense" of the flexibility and infer dynamics from that. Sometimes it feels like an art and a science trying to get meaningful insights for lab data like this.
It's extremely difficult to experimentally verify any MD model since, as mentioned in the article, most of the data we're working with are static mugshots in the form of crystal structures.
Very cool. There are also methods that allow you to extract some notion of motion from variability in CryoEM data, e.g. CryoDRGN-ET [1].
I'm curious if you've worked with any of those models and how they relate to NMR data and MD simulations.
+1 to this!
I've also written a potentially helpful coverage piece on extracting conformations from cryo-EM data: https://www.owlposting.com/p/a-primer-on-ml-in-cryo-electron...
There are also techniques that combine both. In my experience (as an experimental structural biologist working in drug design), they frequently disagree.
That's so cool! What's the software like, compared to say, PyMol? Is it like PyMol, integrated with docking? Are you using MD to position the drugs instead of trying different combos, like Vina does?
hello, I have an undergrad degree in computer science and I'm trying to reach myself informatics to get into this field. do you have any tips, or perhaps an internship available?
if you can reach out at all, you can find me at [masterfully dot blundered] on the normal g-domain. I briefly skimmed your profile for contact info but could not find any.