Umbrella Sampling within a Membrane?

User discussions
1

Hello due to the membrane influence is there a method to perform umbrella sampling with membrane coordinates incorporated? I believe not.

Thanks:)

2

People do umbrella sampling in membrane systems routinely. What problem are you finding, or do you expect to find?

3

Hello and thank you for your kind update and ok great i just need to then scan the tutorials better to understand this methodology, I will update you accordingly if in need:)

4

Membranes do require careful consideration, and you may not find a tutorial directly related to what you want to do, but there have been a huge number of posts about such systems via the gmx-users mailing list and many published studies.

5

Hello and thank you for this kind update and careful direction since the membrane influence is important so I will consider this. I believe Gromacs does not dock a ligand but if gromacs or any other software docks a ligand with membrane included please feel free to let me know which, thanks:)

6

The typical procedure would be to use docking software (indeed, not GROMACS) to generate the complex and then align the complex within the membrane. I don’t know of any docking software that accepts membranes, because they are not generally relevant for doing docking given the approximations of the technique.

7

Hello and ok thank you for your kind update:)

8

Hi Justin I hope you are doing well:),

I am getting closer to my computational investigation, according to our thread after I generate my protein-ligand complex via a docking software outside of Gromacs I was going to run the Gromacs Tutorial 5 Protein-Ligand Complex before aligning the complex within the membrane where I would then umbrella sample. Would you find this methodology of running Tutorial 5 after docking redundant or necessary?

Kind Regards,
Joel:)

9

You need to generate the ligand topology as in Tutorial 5, but I wouldn’t run an MD simulation in water for a membrane protein (or complex). It’s not possible to simply assign your procedure to any one tutorial, you have to combine concepts and adapt the protocols.

10

H Justin thank you for your kind update:)

11

Hi Justin if you know of any transmembrane protein-ligand umbrella simulation studies journaled feel free to refer, I will pubmed search as well.:)

Kind Regards,
Joel

12

…meaning any particular exceptional ones

13

@mjsubach
Hello Joel,
Did you find any tutorial on umbrella sampling of membrane proteins, as I am also stuck at the same point?

Thanks.

14

Hello himanshi09 thank you for your kind inquiry:).

I have docked my ligand to my transmembrane protein and am now in the process of generating the topology for the ligand via Gromacs Tutorial 5, subsequently I will `align the complex within the membrane´ and can then update you accordingly since this would precede the Umbrella Sampling.

Kind Regards,
Joel💡

15

…and no I have not found this tutorial, in this case you may have to just use different publications etc. which is what im doing.

16

Hello

Thank you for your update :)

17

Hi himanshi09 your very welcome:)

18

Hi himanshi09 I hope your well:).

I will be getting closer to completing my ligand topology and then will then align
my transmembrane protein-ligand complex with the membrane, accordingly feel
free to let me know if you completed this task and or discovered any tutorials or
excellent journal articles on this topic, thanks if you did and can:) Joel🚀

19

hello,
Since am also working on protein-ligand complex embedded in a POPC membrane. I have few queries.

  1. first If I want to perform steered molecular dynamics to pull a ligand out of the protein, How to group the atoms, like should I need to group protein, ligand, membrane separately or to group protein-membrane and ligand separately ?
    For note that i have created a index file grouping protein-ligand-membrane and proceeded with equilibration step. If the proceeded step is wrong , Is it possible to modify index file after equilibration step?
  2. what modifications should I need to bring in a code to pull a ligand out of the transmembrane with constant velocity and constant force?
    kindly let me know any relevant articles or publications on this topic. Thanks in advance
20

Hi Sandhya thank you for your kind inquiry:).

For 1. and 2. above are both inquires related to Gromacs Tutorial 3 Umbrella Sampling if not from which of the Gromacs Tutorials are your inquires related to? (I have not reached Tutorial 3 since I am still optimizing a ligand which once complete then I will work through Tutorial 5 Protein-Ligand Complex, once I complete this Tutorial 5 then I will begin to work through the Gromacs Tutorial 3 since firstly I need to build the complex to umbrella sample.) Accordingly feel free to inquire further if any of your inquiries are within the Gromacs Tutorials 1, 2, and or 5 to manage time.

Best,
Joel🚀