[RASMB] Regarding V-bar calculation of peptide containing non-natural amino acid

[Laue, Thomas]

Hi Prasun-

  1.  How different is the atomic composition of your non-natural amino acids from the natural ones?
  2.  Is there any charge present on the aa structure?
If the answers are:

  1.  Not much different
  2.  No
then you can substitute the vbar of the aa with the nearest matching aa.
If the answers are:

  1.  A lot
  2.  No
then you can use the rules determining the vbar from atomic composition and bonding (single versus double). This should get you to ~1% accuracy. There is a table in Cohn and Edsall that can help, and I am pretty sure that there is a similar (perhaps broader) table in the wonderful “Thermodynamic Data for…” book.
If the answers are:

  1.  either not much different or a lot
  2.  Yes
This is where a less accurate result probably will be obtained. You can get a good estimate of vbar from the atomic composition for the uncharged version of the aa. The presence of the charge will decrease the vbar. You might get an idea as to how much it is decreased from the literature. I believe Steve Perkins paper on vbars addresses this. In general, the reduction in vbar due to charge is between 0.05 and 0.08, but there will be uncertainty in how much reduction because of variation due to the aa context. What I have done in the past is simply increase the uncertainty in my measured parameters by varying vbar over a reasonable range.
Best wishes,
Tom

From: RASMB [mailto:rasmb-bounces at list.rasmb.org] On Behalf Of prasun kumar
Sent: Friday, September 29, 2017 3:46 AM
To: Rocco Mattia <mattia.rocco at hsanmartino.it>
Cc: rasmb at list.rasmb.org
Subject: Re: [RASMB] Regarding V-bar calculation of peptide containing non-natural amino acid

Hi Mattia and the group:

Thank You for the response. I installed US-SOMO and just to check whether it is working for peptides with non-natural amino acids, I used one PDB ID (1GOE). It contains DPN and AIB.

Program says it has got unrecognised residues and asked me to take the average value or stop processing......
I chose the first option and got the V-bar value.

Now the question is whether considering the average values for the non-natural amino acids is a good idea or not.... If no then do you think I should also go back and refer to the "bible".

I am doing my experiments in PBS+Water solvent (pH 7.4)

Regards
Prasun

PRASUN (ASHOKA)
Desire + stability = Resolution
Resolution + Hard work = Success

On Thu, Sep 28, 2017 at 10:49 AM, Rocco Mattia <mattia.rocco at hsanmartino.it<mailto:mattia.rocco at hsanmartino.it>> wrote:
Hello Prasun,

if you have a PDB file for your peptide, you can try uploading it in US-SOMO and see if the non-standard AA are recognized and a vbar calculated.

Otherwise, the computations are a bit complicated... we usually do them, when facing non-standard residues, using an Excel worksheet based on the "bible" for vbar calculations:  Durchschlag and Zipper, Prog. Colloid Polym. Sci. 94:20-39, 1994

Hope this helps!

Mattia

________________________________

From: RASMB on behalf of prasun kumar
Sent: Thu 9/28/2017 11:34 AM
To: rasmb at list.rasmb.org<mailto:rasmb at list.rasmb.org>
Subject: [RASMB] Regarding V-bar calculation of peptide containing non-natural amino acid


Hi All:

I have a peptide that contain non-natural amino acids. My query: how to calculate the V-bar of this peptide?
Any suggestions will be really helpful to me.

Regards
Prasun

PRASUN (ASHOKA)
Desire + stability = Resolution
Resolution + Hard work = Success

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