[RASMB] Thanks

[Neil Errington]

Thanks to Tom Laue, Les Holladay, Holger Strauss, Jack Correia and Richard 
Thomas for help & suggestions (summarised below). I can get on and calculate 
the necessary numbers now, though none of the neccesary books are in the 
library here.

The molal volume for CH2 (not CH3) is listed as 16.1 cc/mole by Cohn and 
Edsall "Proteins, amino acids and peptides" (p. 157. The molal volume for H 
is 3.1 cc/mole, which could be added to the value for the CH2, taking into 
account the co-volume. The apparent molal volume of a compound is always 
greater than the sum of the volumes of the constituent atoms or groups 
(these words are almost a direct quote from Cohn and Edsall... a great 
resource)... and the added volume is an empirical term first estimated by 
Traube to be 13 cc/g-mole. That said, the value for C is 9.9 cc/mole, for H 
is 3.1 cc/mole, and for the CH2 group is 16.1 cc/mole, which is the sum of 
the molal volumes of C and 2 Hs. Using the same approach, CH3 would have a 
molal volume of 19.2 cc/mole. 

If we take a slightly different approach, and look at the difference in 
molal volumes for alanine (60.6 cc/mole) and glycine (43.5 cc/mole), the 
estimate for the replacing the H with a CH3 group is 17.1 cc/mole. There are 
differences (of about 0.8 cc/mole) in the electrostriction terms for alanine 
and glycine (gly exhibiting slighly more electrostriction), which affect the 
molal volumes. Even so, 17.1 cc/mole may be a better estimate for what you 
want to calculate (where CH3 is replacing H). 

So, I would increase the molal volume of the methylated amino acids ~17-18 
cc/mole. 
Best wishes, 
Tom 
--------------------------------------------------------------------
Hi; 

I'm attaching three files.  Put them in the same directory, then go to that 
directory and execute setup.exe.  This will unbundle the files and place an 
icon on your desktop.  The program is ProtCalc, and handles some modified 
amino acids. There is a very extensive Word documentation file that explains 
just how I computed the vbar of the mod amino acids. 

If you like this program, I have a CD-ROM full of biophys software I will 
mail you if you e-mail me your snail mail address 

best regards 

Les Holladay 
----------------------------------------------------------------------
There is a very useful table of the volumes of pairs of atoms, list by atom 
and by bond type (e.g. C=0, C-O, C-H, etc.). The table has been reproduced 
several times (it should be on the web!), but the definitive version is in a 
book by Cohn and Edsall "Proteins, amino acids and peptides" Ch. 7. One 
calculates the molar volume based on the structure of the molecule you are 
interested in, then divides by the molecular weight to get the approximation 
of vbar. The values calculated are remarkably close if the material is not 
an ion. There are corrections (reducing vbar) that can be applied for ions. 
There may be a vbar calculated for a compound similar to TAMRA (I presume 
this is a set of conjugated aromatic rings) and that will be a close guess 
for TAMRA. 
Here are some numbers you can use for making a first pass guess: 
Atom/group        Volume (cc/mole) 
        C                9.9 
        H                3.1 
        N                1.5 
        O-                0.4 (2.3 if the second oxygen, as in a carboxyl) 
        O=                5.5 
        NH2                7.7 
        CH2                16.1 
        COOH                18.9 
        CONH (amide)20.0 
For ionization 
  COOH<-> COO-         -10.3 (i.e. decrease the molar volume by 10.3 cc/mole 
for 
each ionized groups) 
  NH3 <-> NH4+     -27.0 
  H2O <-> H+ + OH- -21.0 
------------------------------------------------------------------------
Assuming that your modifications are simply at the termini, the effect on 
vbar should be pretty small even for  relatively short peptides. 
Alternatively, it shouldn't be too difficult to use the additivity 
principle to calculate vbar for the modified constituents and to then use 
these to calculate the overall peptide vbar. There are various tables of 
group contributions - the one I have here is in 'Thermodynamic Data for 
Biochemistry and Biotechnology' (ed Hinz). 
I will admit to simply adding in an extra glycine, on occasion, as an 
approximation for the N-Acetyl, C-Amide case, but don't tell anyone.
-- 
Dr. Neil Errington
Biomolecular Sciences Department
UMIST,
PO Box 88, 
Manchester, 
M60 1QD, UK