Subject: Peptide Rotation Barriers

From: Michael Nolan <[email-masked]>
Date: Mon, 2 Nov 1998 11:26:49 +0000 (GMT)

Hello all,

Thank you to all who amswered my question about rotation about a peptide link.

I had thought that estimating the barrier using only single point calcs would not be valid.
In particular, starting at the trans conformation and stepping along the torsion mentioned below,
at 45^{o} one finds a barrier of over 700kCal/Mol, which indicates a poor geometry (B-LYP/6-31G*).
With PCFF it is even worse......
However that was the only set of calculations I had the resources to carry out (we have one SGI O2 with 
a MIPS R10K 174MHz processor with 128MB RAM and 4GB disk and it runs flat out 24 hours a day)

regards

Michael

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Mr. Michael Nolan	
Materials Modelling Section, Advanced Materials and Technologies Group
National Microelectronics Research Centre  	
Lee Maltings, Prospect Row				   	
Cork
IRELAND

mail: [email-masked]

Tel:   + 353 21 90 4113

http://nmrc.ucc.ie/projects/ape/
http://nmrc.ucc.ie/groups/AMT/modellingRes.html

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http://nmrc.ucc.ie/groups/AMT/SympMain.html
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Original Question....

Dear all,

I'm studying the link formed between p-aminophenol (AP) and p-hydroxybenzoic acid (HBA). The bond formed between
the two molecules is the peptide link 

		X	    O
		 \	   /
	          \	  /
		   N-----C
		  /	  \
		 /	   \
	        H	    X

Now according to the biochemists the most stable conformation is the trans configuration (steric reasons etc etc)
We computed a rotational barrier (trans->cis for HBA-AP), simply by stepping 15 degree incremenets along the
torsion X-N-C-O and calculating single point energies (our resources are so meagre that we cannot do optimisations
for each structure). We used B-LYP/6-31G* and also the PCFF force-field. B-LYP gave a large barrier (hundreds of
kCal/mol) and the FF gave ridiculous results. At least we could see that the barrier to rotation from trans to cis
is very high, which I guess you would expect. 

I have a couple of questions....

1: Would it be in people's opinion valid to use PCFF for MD simulations of this system? Bearing in mind for HBA
we used the PCFF force-field successfully and I guess we would like to be consistent in our use of force-field.

2: Is it valid to estimate the barrier to rotation around the peptide link only from single point calculations?

3: Has anyone looked at this barrier before? I have looked at a number of databases for AP and only got rubbish
and a chemical abstracts search was none too successful. I would appreciate any refs. at all 

Summary as usual

Thanking you for your time

Michael
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Answer 1: