"Clive Delmonte" <clived at ndirect.co.uk> said:
> You mention that the force field calculations give reasonable energies
> for the double helix and that the conformation should be expected quite
> often, but I find myself wondering what that means. The double helical
> conformation should be expected quite often compared to what
> alternatives ?
Energetically speaking, if an unknown but more common conformation
exists, then from a Bolzmann distribution, the binding energy must be
at least somewhat higher than that of a double helix.
(The ratio of the number of states in two different energy states at
equilibrium is = exp(- delta E / kT) .)
The estimate of the binding energy from the free state to the bound
state is known experimentally and is comparable to that predicted by
MD (though there is still a rather large error range and I don't know
a reference comparing them; with all those charges it's a hard
computation).
Thus we have three pairs of energy differences:
free -> double strand
double strand -> conformation X (that required for your proposal)
free -> X
Let's assume the numbers from
http://mills.edu/RESEARCH/FUTURES/JOHNB/structurefunction/708.html
are correct (they are the first I found):
A-T binding is 10 kJ/mol
G-C binding is 15 kJ/mol
For conformation X to exist over 95% of the time requires
0.05 = exp(-E/2.494)
delta E = E(double strand) - E(conformation X) is about 7 kJ/mol
(assuming I got kT right for kilojoules at 300 Kelvin).
That's a big energy difference between them, and given that I don't
think the error estimates from molecular force fields calculations
have that large an error, I cannot believe there is a conformation
that much more energetically favorable than a double stranded model.
Thus, I strongly believe you have misinterpreted the data from the
articles you referenced. As I have not the time, expertise nor
inclination to look them up, I cannot give my own interpretation.
Energy arguments suffice for me to stay with the current model until
someone shows me a predicted structure with sufficient explanatory
power, and you have not done so.
Andrew Dalke
dalke at acm.org
