building complex drug-dna for AMBER software

Question

I will appreciate if you can please clarify some of my doubts about drug-DNA complex.

I want to study the drug-DNA simulation using AMBER. I did go through all the tutorials video on youtube but everything is about protein-ligand using GROMACS. I can also use GROMACS if that gives me the results.

My DNA sequences very small (12-mer) and I want to to intercalate it with a drug molecule. I generated the DNA sequence in Chimera. My questions are as follows.

1. Is it possible to insert my drug at specific sequence and then do the binding energy calculation using AMBER? (1) How can I insert it and make a complex? (2) If I have to create a complex in AMBER how can I do that---reference/tutorials link will be great.

2. The publications I read, they downloaded the PDB file with the drug molecule and extracted the crystallographic information where the drug is attached and then they extended the sequence from there using NAB tools in AMBER. Can somebody please explain how can we do that.

Thank you so much for your time.

1. I want to intercalate the drug molecule at the desired sequence I want and calculate the binding energy.

Answer 1

the tutorials video on youtube

Gromacs has great written documentation, so I'd suggest referring to that directly.

I can also use GROMACS if that gives me the results.

Gromacs works fine with a DNA-ligand system. There are different Amber forcefields, proteins are generally used with AMBER99SB-ILDN simply because it has the longest name and is one of the inbuilt ones. Technically, the Amber forcefield tailored towards DNA is OL15 (recommended here) and gaff2 is for a generalised ff for ligands. These aren't natively within Gromacs, but been ported to Gromacs.

Whereas pi-pi iterations are somewhat covered by the Lenard-Jones term, the orientation will be driven not only by dipole, but also quadrupole moments, which aren't covered by classical mechanics forcefields. Likewise S-pi and cation-pi interactions will not be covered. Most DNA intercalating small molecules have multiple fused rings, e.g. doxorubicin, that pi stack with the DNA. Consequently, a simulation under a classical mechanics forcefield is likely going to be gibberish.

Is it possible to insert my drug at specific sequence

See your previous question and the easiest option of dragging it in PyMOL

Can somebody please explain how can we do that.

Read the AmberTools21 documentation.