What is simulated in 1343x projects?

[ThWuensche]

From JohnChodera's announcement: "These simulations are X-ray structures collected from the COVID Moonshot"

in the 1342x free energy projects, as far as I understand, is estimated, how well and strong different chemicals (ligands) fit into pockets of the main viral protease.

As described in the announcement, 1343x are normal simulations, so normal in the sense of FAH probably means simulations of protein folding, is that right? Does "simulations of X-ray structures" mean that the effect of ligands on the folding of main viral protease is studied for ligand/protease combinations obtained from X-ray cristal analysis to see the effect of these combinations on folding (and thus the behaviour of the main viral protease under the influence of the ligands)?

Or am I completely wrong and the intention of these simulations is different?

[HaloJones]

As some who's been running this project for well over a decade, it pleases me that I still have absolutely no idea what any of the above means

[JimF]

What I find interesting is that FAH seems to have moved beyond its initial charter of studying misfolding, and is now studying how ligands fit into the pockets of a protease. It must make use of the same computational techniques. So they have broadened their horizons. Beyond that, I don't know anything about it either.

[Jonazz]

What I find interesting is that FAH seems to have moved beyond its initial charter of studying misfolding, and is now studying how ligands fit into the pockets of a protease. It must make use of the same computational techniques. So they have broadened their horizons. Beyond that, I don't know anything about it either.

They really stepped up their game when it comes to actually fighting diseases. The first 10-15 years or so were mainly spent on fundamental science - simulating the folding process of a protein from scratch to its final folded state - except for their Alzheimer drug (a shame it wasn't viable, it would have given the project a lot of good press).

But look at where we are now with the techniques they have developed during all those years!

[PantherX]

Normal for F@H would mean that they are not free-energy calculations (that has lots of variability in simulation).

From this article (https://foldingathome.org/2020/05/28/th ... -moonshot/), there are two outcomes from X-ray structures:
1) to get these structures to researchers as soon as they could to aid in finding an effective cure for COVID-19.
2) to see if these compounds bound to the active site of Mpro, and if so, how precisely they were positioned.

I am don't have sufficient knowledge to tell you which ones fits but have a 50% chance at getting it right, assuming the above choices are valid

[bruce]

As some who's been running this project for well over a decade, it pleases me that I still have absolutely no idea what any of the above means

lol

We have to trust the scientists...


Here's what I understand. (I'm sure somebody will come along and correct me if I'm wrong.)

The free energy studies were not well supported by the code that supported traditional misfolding research. The recent updates to Core22 have made such research more feasible. (Thanks, John)

Most of P134xx are free energy studies specificallly for Moonshot. The x-ray diffraction project doesn't really fall into the same category, even though it's also supportive of the Moonshot project so it ended up with a closely related project number.