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I am using classical molecular dynamics (MD) to observe a non-covalent interaction between my complex and the DNA, but there is a problem in that the complex interacts with the terminal of the DNA for a very long time, which is irrelevant in the biological system because the end (terminal) of the DNA cannot be located there. As a result, I want to take some action to reduce the interaction between the complex and DNA. Does anyone know how to help with this problem?

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    $\begingroup$ I would suggest to run multiple simulations, then pick some of them, which is close to the biological case. $\endgroup$ Commented Nov 3, 2022 at 14:54
  • $\begingroup$ @SüleymanSelim I already did that, but it didn't help. $\endgroup$ Commented Nov 3, 2022 at 16:30
  • $\begingroup$ Have you made any progress on this lately? Please update us! $\endgroup$ Commented May 28, 2023 at 2:13
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    $\begingroup$ @NikeDattani. Yes. I will add my answer soon $\endgroup$ Commented May 28, 2023 at 9:57
  • $\begingroup$ @Abd-ElazeemMohamed we're looking forward to it! $\endgroup$ Commented Jun 11, 2023 at 17:26

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Since it has been a month since OP agreed to write an answer without actually writing the answer, I will try answering this.

The easiest way is to perform something called Enhanced Sampling simulations, where you sample along a particular collective variable of interest. If OP knows what the initial and final states are, or between which two sections is the targeted interaction occurring, then the geometric distance between those two sections can be used as the CV for the enhanced sampling simulations.

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I apologize for the delay in responding. I have been occupied with my doctoral studies, and the topic of non-covalent interactions forms a crucial component of my research.

In addressing this matter, we propose the incorporation of harmonic restraints, specifically a repulsive energy, between the drug and the terminal regions of the DNA. To illustrate, in my work, I employ AMBER, and the harmonic restraint is implemented as follows:

 &rst
  iresid=0, fxyz=1,1,1, outxyz=0,
  iat=-1,-1,
  r1=0.0, r2=13.0, r3=13.0, r4=20.0, rk2=65.0, rk3=0.0,
  !! Atoms of the other terminal DNA nucleobases
  igr1=indexes of the nucleobases at the terminal
  !! All drug atoms
  igr2=indexes of all the drug

Instead, we have to apply a positive force constant only on the left side of the parabola:

r1=0.0, r2=13.0, r3=13.0, r4=20.0, rk2=65.0, rk3=0.0,

Now the potential is truly repulsive at short distances and null at long distances.

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