Simulated annealing to investigate conformational change of protein

User discussions
1

GROMACS version: GROMACS 5.1.4
GROMACS modification: No

Dear Gromacs users and developers,

I have an X-ray crystal structure of a protein (~350 amino acids) in an inactive state, and a conformational change is necessary to achieve the active form. (In short: the N-terminal (~50 amino acids) of the protein is blocking the active site, and we know that it must be cleaved for activation to occur. However, we also know that cleavage does not result in dissociation of the N-terminal, therefore we assume that cleavage will cause a conformational change exposing the active site.)

Normal MD simulations have not helped us understand how this occur. I am therefore considering simulated annealing, thinking that the structure might be trapped in a local minima. I have searched for articles where something similar has been done to see what temperatures and time intervals that would be reasonable to start with, but mainly find studies of smaller proteins or peptides, and only for shorter time periods (a few ns).

My questios are:

  • Is simmulated annealing a good option to investigate my problem, or is there any other procedure that you could reccomend me to look into?
  • If simmulated annealing is a good option, does anyone have suggestions on reasonable time intervals and temperatures to start with?

Thank you in advance for any help!

Kind regards,
Cecilia

2

You’re more likely to simply denature the protein by heating it. More refined approaches like enhanced sampling (metadynamics, accelerated MD, etc.) are probably better for this application.

3

Thank you for your reply! I will look into it these methods instead.

Kind regards,
Cecilia