[v.e.akulov]

Hello!

I am interested in performing MD simulation of protein consistent from two parts: disordered tail and folded globule. Additionally  I would like to use course grained model because of big protein size (500 aa).

What do you think, is it possible to parametrized and simulate such a system in GENESIS? If you know how to do this, could you please share with me protocol or give some advises? Thanks!

PS.  I have tried to play with [ cg_IDR_HPS_region ] or [ cg_IDR_KH_region ] parameters, but result was disappointing (protein has lost its structure).

 

Sincerely,

Vasily

 

 

[ctan]

Hi Vasily,

GENESIS 1.7.1 supports CG simulations of proteins consisting of both folded domains and IDRs with some limitations. Excluded volume and electrostatic interactions can be considered between folded domains and IDRs, whereas HPS/KH interactions only apply on IDRs. For inter-chain interactions, the KH model is available, but without the solvent-accessible-surface-area modulation. Although, it is possible to simulate proteins with folded domain and IDR with GENESIS. Actually our group is doing simulations of this kind.

The key is to play with [ cg_IDR_HPS_region ], which you have already figured out. However, telling from what you have described, I guess some local or non-local interactions for the folded domains were lost in your topology file.

Here I give a simple example. Assume that you have a protein (“proA“) with residues 1-20 as a N-terminal IDR, 21-80 as a folded domain, and 81-100 as a C-terminal IDR. To generate topology files, you have to first write a configuration file like this: (let’s name it as “proA.toml“):

[ IDR ] 
HPS_region = "1 to 20, 81 to 100"

then use GENESIS-CG-tool to make the topology files:

aa_2_cg.jl --cgpdb -f proA.toml proA_atomistic.pdb --output-name proA_cg

this will produce files: “proA_cg.top“, “proA_cg.itp“, “proA_cg.gro“, and “proA_cg.pdb“. Particularly, in “proA_cg.itp” you can find several blocks, including “[ atoms ]“, “[ bonds ]“, “[ angles ]“, “[ dihedrals ]“, “[ pairs ]“, and “[ cg_IDR_HPS_region ]“. The “atoms” and “bonds” sections include all the particles, while “angles”, “dihedrals”, and “pairs” involve only the residues in the folded domains (in this example residues 21 to 80). These terms are used to maintain the structure of the folded domains. The last section, “[ cg_IDR_HPS_region ]“, has the information of IDR, in the current case, two lines, “1   20” and “81   100“. Basically, this topology file makes GENESIS know how to treat both folded domains and IDRs with different CG models.

Hope this example can help you. Please let us know if you have further questions. Have fun!

 

Cheng Tan

[v.e.akulov]

Dear Cheng Tan,

Thank you for detailed answer! I will do as you have described.

 

Thanks again,

Vasily