Is it possible to calculate free energy landscape instead of umbrella sampling's PMF?

GROMACS version:2023.2
GROMACS modification: No
Hello, I’m working on a cyclic peptide nanotube and drug system in which the drug transports thorough the nanotube and I’m doing the analysis on it. I wanted to know if it’s possible to get free energy landscapes from PCA analysis instead of getting PMF by doing umbrella sampling?

Dear @shrmi_m

Have you checked in literature for works using PCA for free energy in systems like yours? I guess it really depends on what you want to describe and what is your CV. Also, consider that umbrella sampling is just one of the many ways that you can use to get free energies, so you are not tied to it to calculate the PMF!

With equilibrium sampling you will not sample regions that are a few kT above the free-energy minimum. The main reason for using biased sampling, such as umbrella sampling, is to sample regions with high free energy. If you are not interested in such regions you can use equilibrium sampling. Then you need to map you simulations on some reaction coordinate(s) to obtain free energies. PCA is one (good) option.