AMBER Archive (2008)

Subject: AMBER: Help needed to analyze DNA Holliday Junction - Drug Binding MD simulations.

From: Subramanian Arun Kumar (subramanianarunk_at_gmail.com)
Date: Thu Jan 24 2008 - 11:14:56 CST

Hello,

I am a PhD student in bio-molecular modelling. I have run several 10ns MD
simulations of drug binding to DNA Holliday junctions. For your core idea,
DNA Holliday junctions are higher order 4-way DNA with a junction core in
the centre (you can imagine as two duplex arms connected by a junction).

For understanding structural changes/damage induced by drug in DNA, I am
analyzing:

i) inter-duplex bending which differentiates between two stable
conformations reported namely: open-X and stacked-X which has functional
implications,
ii) changes in minor groove width,
iii) changes in major groove width,
iv) water shell size changes during simulation,
v) ion shell size changes during simulation,
vi) helicoidal parameters using curves algorithm for average structures
representing each nano second (averaged from 50 ps at the end of each ns).

Is there anything else that I can do for enhancing my research? I am
especially interested to study the extent of intra-duplex coiling or bending
in each of the arms. How can I achieve this? Your expert advice will be
appreciated.

Since I found that water shell and ion shell are constantly diffusive in
simulations involving all drug molecules and have no direct or hydrogen
bonded interactions with the dna or drug, i ignored this for compiling my
final report. I have read several papers aimed at studying the structural
changes influenced by ions, but I dont want to do that because they need
more than 75 - 100 ns simulations as they are very time consuming to
converge. I am satisfied by the fact that the ions diffuse although some
numbers stay stable and do not move towards the edge of the box.

Thanking you.

Sincerely,

ArunKumar.

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