Study Folding And/Or Molecular Dynamics Of Just A Flexible Part Of A Protein

Question

[Flow]

In some PDB protein structure I would like to study flexibility in some concrete part of the molecule (small loop). I would like to perform

a) protein folding where all the protein is rigid except the selected part, which remains totally flexible

b) molecular dynamics, where it is only flexible the previously selected part

Although this approach could seem unrealistic, I would like to know which method/programs, etc, would you recommend for performing this.

Answer 1

[dimkal]

The open source/free for academics tools that you may find useful are: a) modeller for loop modelling/refinement and b) NAMD to perform MD with restraints on the part of the protein you'd like to keep rigid.

if you have access to Schrodinger suite, then you can very easily set up the jobs for loop modeling/refinement using Prime and MD with restraints using Desmond.

[Flow]

are there tutorials for my objectives?

[dimkal]

There are great tutorials for NAMD and for Modeller, as well as strong forums or mailing list communities. I'm sure you'll be able to find answers to your questions just by searching the forums. good luck.

Answer 2

[Mitchell]

You probably want to look into GROMACS and preform simulation with position restraints enabled. There is an extensive GROMACS user community and examples should be easy to come by.

[Flow]

are there tutorials for my objectives?

Answer 3

[Khader Shameer]

a) protein folding where all the protein is rigid except the selected part, which remains totally flexible

You already have a PDB file which is indeed in its folded state. Do you want to study the behavior of the specific loop of your protein in different environments like aqueous environment for globular proteins or lipid bi-layers for membrane proteins ?

If this is your goal you may do a position restrain enabled Molecular Dynamics (MD) simulation as suggested by Mitchell. You can use GROMACS for your analysis. Make sure that you enable dynamic behaviors for residues in the loop instead of whole structure. If you are new to GROMACS start with papers and tutorials, also check out How-to, tutorial and search for specific questions in their mailing lists. To get you quickly started here is a direct link on performing simulations But remember that proteins don't behave in such a fashion, loop behavior is often perturbed and influenced by the different parts of a structure.

Instead of doing a full molecular dynamics simulations that will help you find an optimal structural orientation for your loops, you may also do an energy minimization of loops. You can use GROMACS or Rosetta for that purpose. Here is a discussion on how to perform energy minimization of loops using Rosetta. You may also look at literature about Targeted Molecular Dynamics (TMD) that are specifically designed for studying loop dynamics.

See related papers on TMD: 1 Authors studied conformational changes propagate from the ligand-binding site to the pore domain of Nicotinic acetylcholine receptors using NAMD. You can find tutorial for NAMD here and detailed aspects of the simulation methodology in the manuscript.
2 using GROMOS96

b) molecular dynamics, where it is only flexible the previously selected part

I think you are trying to do a MD simulation by specifying specific regions of proteins as you wanted in the first step. There you have used protein folding here you are using the term molecular dynamics. If I understand your analysis context, you are looking at same analytical steps in a and b, it's just that you want to make different regions flexible / rigid.