GROMACS version:2023.2
GROMACS modification: No
The more and more I learn about molecular dynamics the more and confused I get. When I started to learn about different force fields, what type of systems to use them on, and how they affect proteins and ligands. I ran into this idea of force field inaccuracies. Which I then learn that force fields are not perfect, there are errors/imperfections in the way they calculate things energies/interactions between bonded and non-bonded atoms, or interactions between proteins, not taking into account protonation states of residues as the simulation goes on, and etc. Which can all impact your protein stablity and how acurate your model is. Matter of fact it was such a be isssue that I read and article talking about about different refinement methods using restraints, and other attempts too account for force field inaccuracies. Methods for the Refinement of Protein Structure 3D Models - PMC It talked about how because of force field inaccuracies restraints where added during the simulations in order to target certain regions in need of refining to get the model closer to the native/experimental structure and probably other stuff I didin’t get the chance to read because I got side tracked. But with that being said this article was written in 2019, so things might be different know, but I wanted too know is this still a problem in modern day force fields? Has it gotten better? Are there any practical resources that teach you solutions to these issues? Because molcular dynamics doesn’t seem to have as many tutorials covering certain topics like programming does. Are these solutions force field specifc? Also is this something you have to worry about in all simulations? Or just model refinement simulations?
This is not directly a GROMACS question, but I’ll answer anyhow. All models have their limitations. As a scientist, you need to know what the most important limitations of the models are so you can either avoid them or take their inaccuracies into account when interpreting results. Classical molecular mechanics force fields are surprisingly good considering their extremely simplified potentials. Force fields are certainly not perfect, but have been slowly improving over the years. By now they are pretty reliable, but there are still systems or cases where the errors are too large. As a user one should read up on the limitations for the system of interest.
For protonation states there is now a proper solution for GROMACS, but which has not yet been integrated into the main code base:
https://pubs.acs.org/doi/full/10.1021/acs.jctc.2c00516