> I’m trying to simulate a self-complementary oligonucleotide (5 -CTTATGGGCCCATAAG-3 ) by bsc1+TIP3P in 100nM NaCl,
> for 500ns. However, I didn’t observe any secondary structures in the trajectory. I’m wondering if there's anything
> wrong in my production run settings and how do I fix it. The md.in file is attached.
Whether a DNA single strand will fold into a stem loop structure will
depend on the force fields and also the sampling. Before doing any
simulation work on this system, I would peruse the literature to see what
others have done to date.
Earlier work by Chen and Garcia used replica exchange to watch the RNA
UUCG tetraloop to fold w/ 64 replicas each for 300-400 ns.
Work by Chakraborty and co-workers in multiple papers looked at relatively
short 100 ns simulations of different sequences with the CHARMM force
field (c27) and saw collapse but not really stem-loop formation except in
a few cases; really more disordered collapse.
DE Shaw - new force field for single strands -
https://pubs.acs.org/doi/10.1021/acs.jpcb.1c10971
As pointed out in that Shaw paper, the "AMBER" and CHARMM force fields
tend to generate highly compact single stranded structures; however we
have also seen in shorter single strands metastabilty of the B-DNA like
structure on the 500 ns time scale. See also results of Pollack and
Onufriev and also quadruplex folding work by Sponer and colleagues.
I personally would build the sequence into a stem loop structure (based on
a couple of the tetraloop structures available) and see if it is stable in
MD simulation or not, however as I do not think there is a structure known
for the GGCC tetraloop, I would probably study a known tetraloop structure
like GNRA (not UUCG which appears to have troubles with the AMBER force
fields), first.
--tec3
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Received on Sun Oct 30 2022 - 15:00:02 PDT
