> Is it possible to run the terminals at different but fixed protonation
> states without capping ?!!
I think, fixed protonation for the terminal residues should be no
problem. You'd need, however, force field parameters for those residues
as well and those are not included in the standard Amber parameter sets,
AFAIK.
Anselm
>
>
> On Tue, Oct 27, 2015 at 5:34 PM, Jason Swails <jason.swails.gmail.com>
> wrote:
>
>> On Tue, Oct 27, 2015 at 9:32 AM, Hadeer ELHabashy <
>> hadeer.elhabashi.gmail.com> wrote:
>>
>>> Dear Sir
>>> wish you are fine !
>>> It is mentioned in AMBER15 user manual that
>>> " There is currently no support for titrating N or C terminal residues."
>>> And I don't not understand why?
>>> If AMBER can do it for titratable amino acid side chains, why not for the
>>> C- and N terminal ? What is the challenge in this ?!
>>>
>>
>> It requires a *lot* of work, there are significant technical challenges
>> that would need to be dealt with (relating to changing backbone charges
>> introducing sequence dependent reference energies), and the experimental
>> data for amino acid terminus pKa values are less abundant and reliable.
>> For me (I spent my graduate school years working on the constant pH MD
>> methodology in Amber), supporting termini was too much work for far too
>> little benefit to make it worth my while.
>>
>> Add in the fact that the terminal protonation states are *far* less likely
>> to be important for protein structure, dynamics, or function and it is a
>> recipe for not being supported.
>>
>> Is there any other method that can be used for titrating the C- and N
>>> terminals and prepare them for AMBER constant PH simulation ?!!
>>>
>>
>> I'm not sure. Some of the servers (maybe H++ or PROPKA) might give you
>> estimates. And CHARMM might work as well, but I've never tried this
>> before.
>>
>>
>> All the best,
>> Jason
>>
>> P.S., to give a glimpse into the amount of work that would be required --
>> the current CpHMD implementation required creating 2 new residues -- AS4
>> and GL4 -- and required only a single RESP charge fit (deprotonated
>> tyrosine, which wasn't already present in Amber). Supporting termini would
>> require constructing new C-terminal residues for *every* amino acid --
>> about 20 of them -- as well as fitting charges for 40 different residues
>> that do not already have templates (the neutral termini). Then the
>> sequence dependence of the reference energies (caused by the 1-4
>> interactions which are scaled) would probably require separate reference
>> energies for each *pair* of C-terminal or N-terminal residues, which could
>> bring the number of required reference energies to 400... per terminus (by
>> comparison, we have ~10 with the titratable residues supported now). It
>> may not be quite this bad -- there are only 3 different sets of backbone
>> charges, so that 400 may be closer to 60, but there's no way of knowing
>> without trying it.
>>
>> Then you have the complication of how do you treat a C-terminal aspartate
>> or glutamate? That's a very complex residue to assign reference energies
>> for as well, and I don't know that the experimental pKas for the two sites
>> have been fleshed-out.
>>
>> And to keep this all in perspective, the termini are really not that
>> important in the vast majority of cases.
>>
>> --
>> Jason M. Swails
>> BioMaPS,
>> Rutgers University
>> Postdoctoral Researcher
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>>
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Received on Fri Oct 30 2015 - 05:30:03 PDT
