Hi Mary, To further jasons explanation you can easily check the
protonation state in chimera. Just upload the ligand in chimera go to
DockPrep and in add charge part use AM1-BCC charge and you will get
exact protonation state either positive or negative and then run
antechamber with nc 'charge' it will create parameter.
On 6/27/14, Jason Swails <jason.swails.gmail.com> wrote:
> On Fri, 2014-06-27 at 15:05 +0530, Mary Varughese wrote:
>> Sir,
>>
>> In the MD study of target-ligand interaction, if the ligand are acidic
>> compounds like caffeic acid,
>> should i use a formal charge 0 (COOH) or -1 (COO-).
>
> Do you have any evidence for what the protonation state is in the bound
> complex? If so, you should use that.
>
> Otherwise you can try and predict what the protonation state will be
> based on the pKa of caffeic acid and the pH you wish to simulate. Note
> that the influence of the protein can perturb the pKa of the ligand (an
> effect that can be estimated via the use of a thermodynamic cycle as
> shown on page 120 of my dissertation (available here:
> http://jswails.wdfiles.com/local--files/about/jms_Dissertation.pdf).
>
> The pKa of caffeic acid is stated to be 4.62
> (http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:.term+.DOCNO
> +7088). If you want to run at pH 7, it will most likely be deprotonated
> (and negatively charged). If the binding pocket is positively charged
> or has places where a charged carboxylate group can form favorable
> interactions, this will shift the pKa down and make deprotonation even
> more likely. Likewise, a negatively charged environment (which probably
> will not bind carboxylates too well) would have the opposite effect.
>
>> Is anyone familiar with MD simulation involving -ve charged ligands?
>
> This is not at all uncommon.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
>
>
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--
Thanks & Regards;
Soumendranath Bhakat
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Received on Fri Jun 27 2014 - 06:00:03 PDT
