Re: [AMBER] formal charge of the ligand

From: Jason Swails <jason.swails.gmail.com>
Date: Fri, 27 Jun 2014 08:05:29 -0400

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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Received on Fri Jun 27 2014 - 05:30:02 PDT
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