Hi Arvind,

I will recommend you to go through with this link.

https://www.researchgate.net/post/Which_gromacs_force-field_is_to_be_used

Cheers!

Thanks anupama....but i am looking for forcefield which works in docking not MD simulations

Most docking programs (both protein-protein and protein-ligand) use only some features of force-fields, like atom radii, vdW well depths, H-bond radii, perhaps some solvation parameters and that's about it. When docking, there is no need to include the entire force field, since you don't really need the info about the bonds within the molecules (just the non-bonded interaction).

As such most docking programs have their internal sets of parameters, and they can vary a lot. On the other hand they're in many cases based on one of the most popular force fields: OPLS (Schrodinger suite), Charmm or Amber (Dock suite).

For protein-protein (or peptide-protein) docking it can be even simpler: many docking programs use some sorts of simple shape and/orelectrostatics matching. 

I would not be concerned about maintaining uniformity at the docking stage, particularly if you plan to use different programs for ligand docking and for peptide docking (if so, you won't be able to directly compare the results anyhow). You'll probably have to do some MD later to test the stability of the obtained complexes and then you should just use the same force field for these systems.

Thanks Bartosz I got your point. But I have to make some ligands and thereafter I need to minimise their structures. Therefore I need to know any forcefield, which is applicable for both peptides and small molecules.

OK. Both Amber and Charmm have parameters for proteins/peptides as well as a huge number of organic ligands, so stick to them.

Also, I'd say that for small ligands, CHARMM Generalized FF (CGenFF) should be more robust than General Amber FF (GAFF) - note that there are e.g. >50 carbon types in CGenFF and only 12 carbon types in GAFF. But as Bartosz remarked, this will only be relevant if you plan to do some further refinement with more advanced methods.

Can we use mmff94x also?

You may try quantum chemical force fields (ab-initio and DFT).

Mr. Nagi,

Please pay attention on the following papers:

1. Evodiamine and rutaecarpine alkaloids as highly selective transient receptor potential vanilloid 1 agonists, International Journal of Biological Macromolecules, 65,  2014,  314-324, Bojidarka Ivanova, Michael Spiteller

2. Quinoxalines as potent selective CRFRs ligands for monitoring and brain diagnosticOriginal, Bioorganic Chemistry, 58, 2015, 53-64, Bojidarka Ivanova, Michael Spiteller

Hi Arvind,

I think amber general force field GAFF is suitable for you. because antechamber contain parameters for both chemical compounds. The protein-ligand MD is best performed using this force field.

Regards

Mohd Shahbaaz

Hi Negi, the OPLS forcefield works well. Fidele

Thanks @fidele, but i have only MOE which has charmm , amber and MMFF94X. usually i use MMFF94X for small molecules

Do you plan to carry out MD using MOE? I tried before, but the results were not interesting. I later used Amber 

The Amber10:EHT and Amber12:EHT forcefields in MOE include parameters for proteins and nucleic acids and for small molecules and has worked well for the docking simulations I have run with MOE.

the question is whether it will also work well for MD simulations ....

Thanks fidele and sidhir....i will only stick to docking

If you plan to stick to docking, then the AMBER implementation in MOE seems to be OK. Fidele

Thanks fidele, but i was looking for a forcefield which could minimise small molecule and a 51 amnio acid peptide structures. But with these answer, i am confused now which to use and which not to use. Moreover fidele i think amber is better for macromolecular structure and my question was, a forcefield which could be applied to small molecules and peptides too.

MMFF94x

Thanks but when u select this forcefield so it will indicate for only small molecule. Can you confirm me to use it for peptides minimisation.

You can use AMBER for peptides too. The force fields are parameterized to work for individual amino acids; if it works for macromolecular proteins, I see no reason that it should not be the case for peptides.  At least I haven't come across any study that classifies force fields as such.  If anyone has, I would love to go through it.

Regarding the question you ask, I think that you should really try different force fields available to you and see whether there is a consensus. That could be a good way to validate your results. Again, the results obtained in a docking study mostly has little bearing on the force field used and depends a lot on the actual algorithm that the docking program implements. So, its better to maintain uniformity in the docking method so that you can compare results reliably.

. 

I have used this forcefield (MMFF94x) to minimize small molecules as well as proteins before.The degree of precision in energy minimization sometimes depends on the level of accuracy of results expected. Thanks. Fidele

But fidele i think MMFF94x is useful only for small molecules as it doesnt contain all the key parameters required for macromolecule.

Hi Arvind,

I suggest you read the following article on the use of the MMFF94x forcefild in MOE to minimise small molecules in the active site of the 1KV2 kinase:

https://www.chemcomp.com/journal/newscaffold.htm

Thanks

Fidele

Dear Arvind Negi

In the case of docking you can use PFROSST or Amber12EHT for both protein and ligands

Amber12EHT : An all-atom forcefield combining EHT and Amber12. Parameterized for proteins and nucleic acids (ff12) using Amber [Case 2012], and parameterized for small molecules using 2D Extended Hueckel Theory (EHT) [Gerber 1995].

OPLS-AA : for proteins and some small organic molecules

PFROSST: An all-atom forcefield parameterized for proteins, nucleic acids and small molecules. AMBER ff10 parameters are used for macromolecules and parm@Frosst parameters are used for small molecules.

Amber 94, Amber 99 and Charmm 27 are for protein and nucleic acid or DNA RNA not suitable for small ligand or compounds

MMFF94, MMFF94s, and MMFF94x all are for the small organic molecules only the difference is that the conjugated nitrogen, in MMFF94 it is tetrahedral, in MMFF94s it is less tetrahedral, in MMFF94x it is planar

Regards

Tahir

H.E.J research institute of chemistry

University of Karachi

Thanks @ayub!!

Dear Sir,

I believe that CHARMm is of choice for your case.

mmff94x is applicable only for small ligands not peptides.