[gmx-users] antigen-antibody insilico MD using GROMACS

Krzysztof Makuch krzysztof.makuch at gmail.com
Fri Feb 23 17:15:26 CET 2018

If you don't know where exactly binding occurs you can't really do this
using only gromacs. I'd even suggest that until you have to, for antibodies
it might be better to stick mostly to docking software.
1 - you have to have antibody and antigen parametrized using the same
forcefield (FF).
2 - check stability in selected FF. Some make proteins more stable, other
less. It is important to pay attention if your protein really have to be
stable - for example if you take only part of the antibody it may not be
stable either under physiological or in silico conditions. That's why you
may have to use some restrains. Or you may not, you have to decide.
3 - you have to dock antigen in antibody using docking software (there are
many...). Above 50% of results will be ridiculous, often the best energy
still means stupid docking result.
In many cases you may stop here, just use multiple docking engines, compare
and you have supplementary materials for your molecular biology paper. If
you are really stubborn and you have ligand parametrized:
4 - restrain both molecules, equilibrate
5 - turn off restrains and check if your complex is stable. For antibodies
there is quite big chance that it won't be because:
- Ab. is dynamic structure which may change shape after binding and docking
can't simulate this
- Water competes for H-bonds and nobody can guarantee that your complex is
stable enough
- you may have wrong var region.
- the position of antigen may be slightly wrong and in result - break off
7. If everything is ok you can begin energy analysis - umbrella, FEP
In general I advice against being stubborn until this is your primary
project. Antibodies are nasty, little guys.

2018-02-23 15:24 GMT+01:00 Deep kumar <deepak.choubey86 at gmail.com>:

> Hi Gromacs users,
> I am studying antigen-antibody interaction at protein level. I have a
> protein sequence (no crystal structure, length 180 residues) of the
> antigen, and have predicted the secondary structure of it (and modeled). By
> performing conserved domain search using inferno and NCBI I found out a
> domain in the antigen - PCC1 (residue 90 to 160). I am interested to know
> how the antigen interacts with the antibody (2000 residues) *in silico*.
> The ultimate aim is to find out "how the antigen interacts with the
> antibody, and predict the possible domains used by the antigen to interact
> with the antibody". I would really appreciate your valuable suggestions on
> how this can be done using GROMACS MD. Please let me know if I need to
> provide any further information. Thanks for your time.
> Regards,
> DK
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Jagiellonian University
Department of Computational Biophysics and Bioinformatics
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