AMBER Archive (2006)

Subject: Re: AMBER: MD of oligomer sequences

From: David A. Case (case_at_scripps.edu)
Date: Thu Feb 02 2006 - 20:08:42 CST

On Thu, Feb 02, 2006, Atilio I Anzellotti/O/VCU wrote:
>
>
> I am modelling two DNA oligomers both 20 base pair long. One of them has
> 9 T-A base pairs and the other 11 T-A base pairs. According to
> experimental data, the former should be more stable according to an
> expected higher Tm point. The problem is that after 1.2 ns simulation the
> energy of the former (9 T-A) is -61kcal while the other (11 T-A)
> exhibited -65kcal which is the opposite to what I would expect, both
> values for total energy are stable.

There is no reason to expect the total energy to have much of anything to do
with melting temperatures. Even in the simplest of models, the thermal
stability of a sequence is related to *difference* between the duplex state
and its thermally denatured state. You would need to run simulations on the
unfolded forms of your two sequences, and take differences, to get something
akin to what you want.

The above discussion ignores the difference betwen free energy (which is what
you really want) and the average of the potential energy, which may be what
you are quoting. This can be a very non-trivial difference. Using
computation to estimate melting temperatures of nucleic acids is a *very*
difficult problem. Some reader on the list may correct me, but I believe it
is essentially still an unsolved problem....

....dac

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