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Re: WSN: hidrophobic/Van der Walls interactions energy... (fwd)
Sender: haney@netcom.com (Dr. David N. Haney)
Subject: Re: WSN: hidrophobic/Van der Walls interactions energy...
Kahn writes:
>..Replacement of the normal glutamate at the beta six position by valine
>does create a hydrophobic patch on the surface of the protein. This causes
>the protein to polymerize in a reversible entropy driven process. The normal
>protein, however, does not polymerize...
I apologize if I missed an important part of previous discussion on this
topic. I also have been working under an important deadline. I have studied
sickle hemoglobin both in the lab and using computational tools. Yes you can
demonstrate computationally, the hydrophobic region that is generally
described by inspecting the fiber structure. However, I think it would be
difficult to calculate the free energy value for this mutation. You can use
a program like HINT (which is based on empirical hydrophobicity methods from
Leo, Hanch and Abraham) to calculate the approximate hydrophobic and hydrophilic
contributions to an interation, but it is a far cry from giving you free
energy values. There is a great deal of literature on the biophysics of
this system from Hofrichter, Eaton and Moffat. In fact, I thought that
one of their papers indicated that normal hemoglobin, HbA, could
aggregate if the Hb concentration was high enough and the salt concentration
was low enough.
In a computational study in which I evaluated the potential energy of various
residues in the crystal fiber, I found that while the process may be driven
by hydrophobicity, there are clear electrostatic interaction contributing to
the stablity of this fiber. Sone of these interactions are in the same area as
the mutation at Beta Lys 8 which interacts with the proprionate of the heme
in the adjacent molecule. Clearly additional solvent methods would be a
benefit, but we must be able to account for salts and solute concentration
to make free energy predictions based on atomistic parameters.
--
************** David N. Haney, Ph.D. ****************
* Haney Associates Phone - 619-566-1127 *
* 12010 Medoc Ln. *
* San Diego, CA 92131 Fax - 619-586-1481 *
************** Email - haney@netcom.com ***************
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