Suggestion on Peptide Model Preparation

GROMACS version: 2020.4
GROMACS modification: No

I have created a peptide using Discovery Studio, which gave me a straight chain. Since no peptide exists in a shape of a straight line, I ran MD simulation for 300 ns and applied clustering on the last 100 ns to find the representative structure.

Problem was, the “prepared” structure had rather compact shape with a B-sheet, and the structure was already quite stable that after I ran the actual simulation with other molecules, the shape didn’t change much.

My question is: When you are using a peptide model that you made from scratch and want it to rather have a random-coiled structure (instead of a straight line), what do you suggest to do?

Thank you.

A few clarifying questions:

  1. What evidence do you have that the peptide shouldn’t have beta-structures?

  2. What force-field/simulation settings are you using? Different force-fields have differing degrees of accuracy in reproducing the structural ensembles of peptides. Additionally, single long-simulations may get “stuck” in meta-stable states, enhanced sampling techniques are often necessary to avoid this if (H-REMD is one option, simulated annealing or T-REMD would also be reasonable options, albeit H-REMD and T-REMD)

  3. If you are just trying to prepare your peptide for other simulations, have you considered using something like pep-fold ( PEP-FOLD Peptide Structure Prediction Server) or iFold (iFold: Interactive Folding) to generate your initial structure rather than starting with a completely extended chain?

  4. If you just want to make a random coil, when you are building the peptide, I presume (I’ve not used Discovery Studio and I don’t have access to a copy) you should have an option to assign dihedrals as you ‘grow’ the peptide. If you select phi/psi combinations that are not in the beta or helical regions of the ramachandra space (see: Ramachandran plot - Wikipedia ) that should, ideally, give you a “random coil”


Thank you for the reply. To answer some of your questions:

  1. My PI told me to try MD simulations using the peptide with a random coil structure.
  2. I have been using AMBER 99SB-ILDN forcefield. I guess I should try to look into how to do the REMD.

3 - 4. Both actually. I want to start the MD simulations with randomly-coiled peptide that doesn’t have completely extended structure and stabilized secondary structures.