Hi,

I’ve recently started investigating receptor-ligand interactions using peptides as ligands. My approach involves docking to determine the initial binding pose, followed by molecular dynamics (MD) simulations to evaluate the behavior over time.

In my current study, I’m analyzing three peptides interacting individually with the same receptor. However, the RMSD values between the peptides’ heavy atoms and the receptor’s backbone range from 1 nm to 3 nm, which I find unusually high. Upon visualizing the trajectories, I notice behaviors such as one peptide maintaining close contact with the receptor while another appears to drift away, seemingly attempting to dissociate. If this reflects the actual dynamics, that’s fine—data is data—but I suspect there might be methodological issues at play.

I’m performing all-atom simulations (300 ns) in a cubic water box (TIP3P) using the CHARMM36 force field.

Those who have experience with protein-peptide MD simulations: what steps could I take to improve the quality or reliability of my simulations?