Hi All,
I want to find the energy for the polypeptide chain which has the N terminal has NH2 and C terminal has COOH. I used charmm22 ff and by default it takes as zwitter ion and with patch first and last none it consider the polypeptide chain as NH and CO. Is there a way to treat the sequence with NH2 and COOH end caps?

One more question : How to neutralize the sequence having (more lys or/and arg) net positive charge, without adding counter ions?
For the net negative charge, I used patch for Asp and Glu residues.

I will be thankful for any suggestions/comments.

Varsha

In line with what's been done in experiments, there are neutral acetyl and methylamine end patches. The CHARMM force field tends to focus on dominant aqueous species.

I think questions about rare neutral species may have been answered before, perhaps in the more relevant Parameter Set forum. Have you tried the Search feature of these forums?

Hi Rick,
Thank You for your suggestions. I saw in the parameter set forum. But still I didn't have the solution for neutral ARG. I saw only the acetylated N-terminus and methylated C-terminus but no NTER/CTER with this kind of NH2 and COOH in the topology files ( within c33b2 package). I performed the calculations with zwitter ion, but to check whether there is much energy changes due to this end caps in my prediction.

Thanks in advance for any helpful suggestions/comments.

Varsha

Note that you can always download the most recent rtf/parameter files from the MacKerell website. There you will find NNEU and CNEU patches in top_all22_prot. A neutral ARG along the same lines as for LYS and ASP is a little more complicated since one has to decide which proton to remove; based on model compound calculations (J. Norberg, N. Foloppe, L. Nilsson, Intrinsic Relative Stabilities of the Neutral Tautomers of Arginine Side-Chain Models, J. Chem. Theor. Comp. 1 (2005) 986-993) the proton on NE seems to be the most likely candidate.

An alternative, since you are anyhow aiming for an unphysical situation with all titratable groups neutral at the same time, is to look at the neutralization in the eef1 files in support/aspara.

Thank you for suggestions and quoting your paper. I will download and try with recent toppar files.


Varsha

Model compounds for neutral arginine side chains were once built in the framework of CHARMM22 but they were never properly optimized. They were mistakenly included in the toppar/stream directory of certain CHARMM force field distributions but are not in the current one. An improved version of those same parameters is currently in use for the model compounds RESI MGU1 and MGU2 in the CHARMM General Force Field (CGenFF). Following Lennart's paper, MGU1 represents the most likely candidate. If you really insist on simulating neutral arginine, you can try to transfer the parameters back from CGenFF to the protein force field. The usual caveats apply; in particular, the compounds from CGenFF might not meet the protein force field's standards. In my opinion, it's not worth all that effort just to construct an physically unlikely state, but you're free to do it nevertheless

I still don't fully understand what your goal is, but perhaps it would be better to do a simulation with the backbone in zwitterionic state and the side chains charged "as in physiological pH", and a second simulation with the same side chain protonation state but with the N and C-terminus capped with amides. That way, you're comparing two physically relevant species with the same net charge and you don't have to add or remove counterions.