GROMACS version: 2022
GROMACS modification: No
Hello everyone.
For my PhD project, I want to investigate the permeation of different nanoparticles through different model cell membranes. For this purpose, after conducting the SMD simulation, I will compare the PMFs obtained from umbrella sampling.
In this regard, the reviewer of my proposal asked some questions that I have to answer on the day of my defense and I would be grateful if you could help me find the best answers:
1- since my system is for the first time to be studied and i do not have experimental data, how can i understand that the resulted PMF and free energy is valid?
2- Is the umbrella sampling method acceptable in terms of thermodynamics and statistics just in certain conditions? What do these conditions include? How should my system be discussed in this regard?
3- As the method of obtaining free energy in my studied system is non-equilibrated, what are the necessary conditions for verifying the correctness of non-equilibrium methods in this study? How can Jarzynski’s equation be used in this regard?
(He told me that by Jarzynski’s equation, I should check How my system is thermodynamically in the right condition and does not collapse and how the results fit into the criteria that show whether the free energy taken is valid or not, and in general, what are the valid thermodynamic conditions for my system?)
How can I get to the answer to this question without doing Jarzynski’s Equality and just theoretically?
Steered Molecular Dynamics (SMD) and Umbrella Sampling (US) are two different techniques.
Usually, the Steered Molecular Dynamics implementation of the Jarzynski Equality (JE-SMD) exaggerates the PMF values and is often more suitable for comparison purposes. To enhance accuracy, one can adjust parameters such as spring stiffness or adopt a slower pulling rate, albeit at the expense of requiring a longer time step and consequently incurring higher computational costs. more information: Calculating potentials of mean force from steered molecular dynamics simulations. It is better to show the pulling path of all replicas using JE-SMD in your results to demonstrate that the system is not deviating from the desired CV.
P.S. You can pull your system in GROMACS, but SMD is not a GROMACS tool. you can ask more in the relevant forum.
**Regarding Umbrella Sampling (US) **, I need more information (about how you performed US in GROMACS) to answer your questions.
Alternatively, you can use Accelerated Weight Histogram method (AWH) in GROMACS, which requires fewer parameters to set and is user-friendly. AWH tutorials are available on GROMACS website: Potential of mean force using AWH method
Dear farzane. thank you for your comments.
about SMD, i meant that after pulling, i will do US. i mean i do US after pulling step.
this is my pull code:
; 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 = direction
pull_group1_pbcatom = 54
pull_coord1_vec = 0.0 0.0 1.0
pull_coord1_rate = 0.0001 ; 0.0001 nm per ps = 0.1 nm per ns
pull_coord1_k = 3000 ; kJ mol^-1 nm^-2
i do not want to do Jarzynski Equality, i just want to know how can i use Jarzynski Equation to know if my system is in a suitable state thermodynamically and my results will be valid.