Re: [AMBER] formal charge of the ligand

From: Soumendranath Bhakat <bhakatsoumendranath.gmail.com>
Date: Fri, 27 Jun 2014 18:03:59 +0530

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
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