AMBER Archive (2009)

Subject: Re: [AMBER] DNA + intercalator

From: Ashish Runthala (
Date: Fri Jul 24 2009 - 22:12:27 CDT

Bill is correct about that normal simulation. But one thing you can do.
I guess do these steps.
1. Run Sirius to exactly trace the locus where the drug intercalates.
2. Now study the base pairs top and below the drug 'buckle', to study their
resultant drifted conformation, due to drug binding. This can be studied
better by studying the prevention of association of DNA helicase,
topoisomerase, and polymerase enzyme families, which should definitely bind
in the native initial confirmation.
3. To design the structure, use that DNA sequence, to compare with any known
sequences, whose structures are known, like PSI-BLAST.
4. Design the structure, do minimization with explicit solvent in amber.
5. Once you have located the interaction sites properly and you have the
minimized confirmation of the structure, use ibelly=1, with bellymask in
AMBER, to study the simulation, keeping the salt level similar to the *
in-vivo* condition as per your desired organism. Do a large production run
at the end with very small time steps, to study it better.

Good Luck ,

The base pairs above and below the drug 'buckle' in conformation to afford a
distorted DNA helix thereby preventing association with the DNA
DNA topoisomerase<>
3 and polymerase families of enzymes to initiate DNA replication for RNA
synthesis, protein formation and thereby cell division.

On Sat, Jul 25, 2009 at 8:03 AM, Bill Ross <> wrote:

> > We dont have anyinitial structure
> > and I know that I can use Sirius to manually dock the drug, but,
> > where to begin? Outside of the DNA? Starting with the drug already
> > intercalated in the DNA? Near the PO4- group?
> If the drug intercalates between bases, I would start with it intercalated
> because it will probably not achieve that state in normal simulation
> times.
> Bill
> _______________________________________________
> AMBER mailing list

Ashish Runthala,
Faculty Division III,
Lecturer, Biological Sciences,
Birla Institute of Technology and Science,
Pilani, Rajasthan- 333031
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