Hi Friends,
As I wanted to do structural studies of amonafide with the DNA sequence D(CCTGGTCC):D(GGACCAGG), I have done MD simulation in Gromacs with the force field amber99sb ildn. This DNA sequence has been extracted from the pdb which was bound with the cisplatin (also no experimental evidence for the specific sequence with amonafide). Initially, I have done a simulation for 50ns time period with the topology which was produced by acpype. In the trajectory, i could see the fine structures at 10ns, 40th ns and small disruptions in 50ns, but during the 20,30th ns there was complete disruption in the structures. Then I wanted to do the same simulation for 100ns from the initial structure. I was scared I got completely different structures without doing any changes in the topology and force field. Then the same input has been submitted in yasara provides quite different structures.
1. What could be the reason for this?
Also, I suspected my topology and added RESP charges (produced by R.E.D) with the same topology and doing the simulation again. Now also I could see the disrupted DNA during the simulation. There are some results for the denatured DNA which would be actually possible after 200ns. So I want to know that,
2. Is this because of the topology issues or because of the drug with that DNA sequence ?
3. Should I concentrate on charges again?
I want you to help me with this issue. I also attached the structures for your perusal.
Sincerely,
R. Radhika
Hi Radika, Can you post the picture of DNA when you say it is 'disrupted'. Maybe, it could be something to do with imaging of the trajectory. Also, If just fraying of terminal bases, that is normal and can be taken care using mild restraints. if you see unusual torsion angles or bond lengths in the residues that are related to ur ligand then it has something to do with the parameters you have generated. If the ligand is placed in a wrong way close to the DNA with steric clashes and intertwining that will also lead to disruption.
what is the netcharge of your system? did you add (counter)ions? if so, which, how many, and where? ... also gaff (what you get from acpype) is probably not an optimal choice for DNA. simulations. there are specific sets of DNA parameters for all major ffs. you better use one of these.
Dear Dr. Senthilkumar Kailasam,
I already attached all the pdb files which i tried for so many times (structures.zip) Please have a look at these and I need your kind suggestion.
With regards,
R. Radhika
Dear Dr. Jamoliddin Razzokov,
Thanks for the suggestion.
With regards,
R. Radhika
Dear Dr. Michael Brunsteiner,
I have added counter ions and made the neutral system as in the gromacs tutorial. If GAFF is not the right choice then what could be the right option (any web portal) to do that ?
With regards,
R. Radhika
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