How to study an ATPase conformation using molecular dynamics

rpestana94

Hi, I want to study how a protein, an ATPase, change its conformation, from E1 to E2 and again E1, for this, I have read that targeted molecular dynamics (TMD) or metadynamics can help me, I want to know if there is another way to do it or any software that you recommend to do it.

Also want to study the phosphorylation in this protein, in this case, to pass from E1 to E2 I need to phosphorylate the protein, in this particular event is better to use QM/MM to see how this reaction is occurring or there is another alternative?

Here is an example of how the circles in an ATPase protein works, I want to explain it using molecular dynamics, any advice is welcome.

sobereva

QM/MM is not needed if you are not interested in phosphorylation reaction. To study how phosphorylation changes the protein conformation, you can simply mutate the native protein and then conduct standard MD simulation to observe the change in conformation.

rpestana94

sobereva 发表于 2021-8-28 01:40
QM/MM is not needed if you are not interested in phosphorylation reaction. To study how phosphorylat ...

Thanks, in the case of trying to do a QM/MM is there any post from you about considering what to use?

I think, not sure, usually, when people use QM/MM approach, the basis set is lower than using QM alone, I assume for the number of atoms when we use QM are really small molecules.

sobereva

rpestana94 发表于 2021-8-30 22:46
Thanks, in the case of trying to do a QM/MM is there any post from you about considering what to u ...

You can use basis set as regular quantum chemistry studies. However, considering that QM/MM MD needs to calculate a large number of frames, so the employed basis set should not be too large. Usually 6-31G* and def2-SV(P) are inexpensive and acceptable choices.

rpestana94

sobereva 发表于 2021-8-31 00:30
You can use basis set as regular quantum chemistry studies. However, considering that QM/MM MD nee ...

Thanks

Christ

It's really an interesting study, similar to what I'm doing now, that's why I'd like to ask for help here.

My project is about the catalysis of ATP in a kinase pocket, and I'd like to observe in a kinase which residue contributes more to the phosphorylation, and which kinase could perform the phosphorylation with a lower energy barrier. I'd like to ask for a potential basis set for it.

As a fresh in the Gassuian, maybe my question is naive, I'm sorry for wasting your time and looking forward to your invaluable reply! Thanks

rpestana94

Christ 发表于 2023-11-30 01:27
It's really an interesting study, similar to what I'm doing now, that's why I'd like to ask for help ...

if you try doing QM/MM what the professor suggest I think is the best option, for just QM of the pocket I'm not pretty sure which can be the best method.