# Question from umbrella sampling **URL:** \ **Category:** User discussions\ **Tags:** umbrella-sampling\ **Created:** [September 27, 2023, 12:25pm UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278 "2023-09-27T12:25:00Z")\ **Posts on this page:** 7\ **Page:** 1
**Author:** ![mahisan](https://avatars.discourse-cdn.com/v4/letter/m/ee7513/32.png) [@mahisan](https://gromacs.bioexcel.eu/u/mahisan)\ **Post date:** [September 27, 2023, 12:25pm UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/1 "2023-09-27T12:25:00Z")
GROMACS version: 2022 GROMACS modification: No hi everyone. i am a beginner PhD student in the field of md simulation and want to use umbrella sampling to study the permeation of my nanoparticle through a membrane. my system contains “ions, water, nanoparticle and membrane” i prepared 2 groups in my index file: (1) nano | (2) other (contain membrane, water and ion). is it correct as i just want to pull my nanoparticle? so is this pulling code in my mdp file ok or i should modify it? ; Pull code pull = yes pull\_ncoords = 1 ; only one reaction coordinate pull\_ngroups = 2 ; two groups defining one reaction coordinate pull\_group1\_name = other pull\_group2\_name = nano pull\_coord1\_type = umbrella ; harmonic potential pull\_coord1\_geometry = direction ; simple distance increase pull\_coord1\_vec = 0 0 1 pull\_coord1\_dim = N N Y pull\_coord1\_groups = 1 2 pull\_coord1\_start = yes ; define initial COM distance \> 0 pull\_coord1\_rate = -0.01 ; 0.01 nm per ps = 10 nm per ns pull\_coord1\_k = 1000 ; kJ mol^-1 nm^-2 thank you for your consideration. ---
**Author:** ![hess](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/hess/32/416_2.png) [@hess](https://gromacs.bioexcel.eu/u/hess)\ **Post date:** [October 3, 2023, 4:35pm UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/2 "2023-10-03T16:35:39Z")
If you want to pull a nanoparticle through a membrane, you should not pull on everything else. You should use: pull\_group1\_name = membrane pull\_group2\_name = nano pull\_coord1\_geometry = cylinder But a nanoparticle sounds too large to get good sampling for. In addition your setup currently does steered MD, not umbrella sampling. It might be good to look at a tutorial first. ---
**Author:** ![mahisan](https://avatars.discourse-cdn.com/v4/letter/m/ee7513/32.png) [@mahisan](https://gromacs.bioexcel.eu/u/mahisan)\ **Post date:** [October 5, 2023, 9:06am UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/4 "2023-10-05T09:06:58Z")
dear hess, thank you for your reply. you are right i first wanted to do SMD, and then umbrella sampling. i am simulating my self-assembled nanoparticles first which have about 3nm diameter. my membrane has 4 nm thickness. do you think that this condition may not a have good sampling result? so what should i do? i modified my code in such way: is it good? ; Pull code pull = yes pull\_ncoords = 1 ; only one reaction coordinate pull\_ngroups = 2 ; two groups defining one reaction coordinate pull\_group1\_name = membrane pull\_group2\_name = nano pull\_coord1\_type = umbrella ; harmonic potential pull\_coord1\_dim = N N Y ; pull along z pull\_coord1\_groups = 1 2 ; pull\_coord1\_start = yes ; define initial COM distance \> 0 pull-pbc-ref-prev-step-com = yes pull-coord1-geometry = cylinder pull\_coord1\_vec = 0.0 0.0 1.0 pull\_coord1\_rate = 0.0001 ; pull\_coord1\_k = 1000 ; kJ mol^-1 nm^-2 ---
**Author:** ![hess](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/hess/32/416_2.png) [@hess](https://gromacs.bioexcel.eu/u/hess)\ **Post date:** [October 5, 2023, 9:43am UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/5 "2023-10-05T09:43:17Z")
Theoretically this should work. But I think that in practice it is unlikely that you will get sufficient sampling for a particle of 3 nm diameter. Note that you would need to increase the cylinder radius pull-cylinder-r to be significantly larger than the radius of your particle. ---
**Author:** ![mahisan](https://avatars.discourse-cdn.com/v4/letter/m/ee7513/32.png) [@mahisan](https://gromacs.bioexcel.eu/u/mahisan)\ **Post date:** [October 14, 2023, 8:32am UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/6 "2023-10-14T08:32:42Z")
Dear hess. thank you so much. i have now another question, besides umbrella sampling, which kind of other sampling ways may be a good choice for my system? is Adaptive weighted histogram (AWH) method a good one in this case? The goal here is to just compare the interaction and permeation of different nanoparticles through a model cell membrane to identify which one is more favorable than another. If yes, is there a tutorial like this tutorial for umbrella sampling that describes the exact steps of how to do this method and how to prepare the relevant files and commands (not necessarily basic and general concepts)? ([Umbrella Sampling](http://www.mdtutorials.com/gmx/umbrella/index.html)) And whether the results of this method will be comparable to umbrella sampling in the end? ---
**Author:** ![mahisan](https://avatars.discourse-cdn.com/v4/letter/m/ee7513/32.png) [@mahisan](https://gromacs.bioexcel.eu/u/mahisan)\ **Post date:** [October 14, 2023, 8:33am UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/7 "2023-10-14T08:33:02Z")
Dear hess. thank you so much. i have now another question, besides umbrella sampling, which kind of other sampling ways may be a good choice for my system? is Adaptive weighted histogram (AWH) method a good one in this case? The goal here is to just compare the interaction and permeation of different nanoparticles through a model cell membrane to identify which one is more favorable than another. If yes, is there a tutorial like this tutorial for umbrella sampling that describes the exact steps of how to do this method and how to prepare the relevant files and commands (not necessarily basic and general concepts)? ([Umbrella Sampling](http://www.mdtutorials.com/gmx/umbrella/index.html)) And whether the results of this method will be comparable to umbrella sampling in the end? ---
**Author:** ![hess](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/hess/32/416_2.png) [@hess](https://gromacs.bioexcel.eu/u/hess)\ **Post date:** [October 16, 2023, 6:17am UTC](https://gromacs.bioexcel.eu/t/question-from-umbrella-sampling/7278/8 "2023-10-16T06:17:01Z")
As i expect the long timescales involved to be the issue, I don’t think AWH will help much. AWH can use the same pull setup as umbrella sampling with a few extra AWH parameters. A tutorial for DNA base pair opening can be found here: [Calculating PMFs with AWH in GROMACS — GROMACS tutorials https://tutorials.gromacs.org documentation](https://tutorials.gromacs.org/docs/awh-tutorial.html)