3 ms·

Do you know how they deal with DNA? Does it fit in a single voxel? (Probably no). Are strands of DNA and RNA treated in chunks in a chain of voxels? Does the si

Do you know how they deal with DNA? Does it fit in a single voxel? (Probably no). Are strands of DNA and RNA treated in chunks in a chain of voxels? Does the simulation perform transcription?

blix 5y ago
I am not an expert on this type of model but after reading their methods section a little more thoroughly, this is my sense: I don't believe there is any case where a molecule in one voxel knows about molecules in other voxels. DNA and RNA is coarse grained where a 'molecule' might represent a specific sequence of interest rather than a full chain. Transcription and translation are modeled, essentially by saying if the neccessary ingredients are present in a voxel (DNA/RNA sequences, enzymes, raw materials, etc) there is some chance of forming mRNA or a protein as a function of the molecular concentrations present in the voxel. DNA and RNA reactions are treated with somewhat different equations than the rest of the molecules, I think to handle the coarse graining.
- tmearnest 5y ago
  This is all correct. These simulations actually can model molecular crowding by using a diffusive propensity proportional to the particles in the adjacent cells but I don’t think it was used here. I developed this methodology in grad school, but it didn’t go any where.
  - blix 5y ago
    Thanks for confirming my take. This is a little out of my comfort zone. Do you see a future for this simulation method with increased computing power, or do you think limitations of the method might still limit its applicability. Maybe this is naivete coming from atomistic perspective, but it seems to me that the inability to model reactions that aren't explicitly predefined would be a significant challenge.
tmearnest 5y ago
Dna does not fit in a voxel. Transcription is modeled by particles fixed in space which produce transcripts at a constant rate. The mRNA is treated the same as the other discrete particles in the simulation, though they are likely a bit bigger than the voxel size.

Do you know how they deal with DNA? Does it fit in a single voxel? (Probably no). Are strands of DNA and RNA treated in chunks in a chain of voxels? Does the simulation perform transcription?

blix 5y ago

I am not an expert on this type of model but after reading their methods section a little more thoroughly, this is my sense: I don't believe there is any case where a molecule in one voxel knows about molecules in other voxels. DNA and RNA is coarse grained where a 'molecule' might represent a specific sequence of interest rather than a full chain. Transcription and translation are modeled, essentially by saying if the neccessary ingredients are present in a voxel (DNA/RNA sequences, enzymes, raw materials, etc) there is some chance of forming mRNA or a protein as a function of the molecular concentrations present in the voxel. DNA and RNA reactions are treated with somewhat different equations than the rest of the molecules, I think to handle the coarse graining.

tmearnest 5y ago
This is all correct. These simulations actually can model molecular crowding by using a diffusive propensity proportional to the particles in the adjacent cells but I don’t think it was used here. I developed this methodology in grad school, but it didn’t go any where.
- blix 5y ago
  Thanks for confirming my take. This is a little out of my comfort zone. Do you see a future for this simulation method with increased computing power, or do you think limitations of the method might still limit its applicability. Maybe this is naivete coming from atomistic perspective, but it seems to me that the inability to model reactions that aren't explicitly predefined would be a significant challenge.

tmearnest 5y ago

Dna does not fit in a voxel. Transcription is modeled by particles fixed in space which produce transcripts at a constant rate. The mRNA is treated the same as the other discrete particles in the simulation, though they are likely a bit bigger than the voxel size.