Hi
Can please tell me, To analyze the results of molecular docking and simulation of molecular dynamics (MD) of enzyme and ligand in Gromacs, what other analyzes can be done on them that can be discussed as a separate issue, except for usual analyzes such as RMSD, RMSF, Radius of Gyration, PCA, Gibbs free energy, GMMPBSA?
Thanks a lot
Separate issue or separate publication? How long simulation do you have or you are going to conduct?
Most of the time, people are interested in the binding energy of ligand, however, ligand dissociation pattern, key atoms when ligand approach the protein, conformational change in ligand, and allosteric movement in protein in response to ligand binding etc.
Ayaz Anwar Yes, separate publication.
100 ns
Thank you very much for your answer
100ns is less, you should run for longer or repeat it 2more times. Good luck.
Ayaz Anwar Thank you for your answer.
Yes, I repeated some simulations 2-3 times.
To check the allosteric allosteric movement of enzyme and ligand, what analysis do you suggest?
What do you mean by "ligand dissociation pattern" ? That is, after the enzyme has done its catalytic action, we should check how the ligand is separated from the enzyme?
Thank you very much
For allosteric, you can see this publication:
Motions of Allosteric and Orthosteric Ligand-Binding Sites in Proteins are Highly Correlated | Journal of Chemical Information and Modeling (acs.org)
https://www.nature.com/articles/s41467-020-17618-2
You can even perform Residue Interaction Network analysis:
RING 3.0: fast generation of probabilistic residue interaction networks from structural ensembles | Nucleic Acids Research | Oxford Academic (oup.com)
"ligand dissociation pattern" > (1) Just look into the distance between ligand and protein atoms and see what atoms dissociates first? (2) Does ligand rebinds with the protein or it just leaves [this may not be possible given the length of simulation, but give it a try], (3) Contact intensity of ligand atoms towards the protein atoms, (4) any atom makes/change contact for longer time or change frequently, (5) angle between ligand atoms; do they change and to what extent. etc
Ayaz Anwar Your answer is very helpful
Thank you very much
best regard for you
Besides standard analyses like RMSD, RMSF, and PCA, other useful analyses for molecular docking and dynamics include decomposing binding free energy, analyzing hydrogen bonds, studying protein motion via PCA, investigating hydrophobic interactions, examining water dynamics, constructing residue interaction networks, identifying allosteric sites, analyzing binding pathways, assessing solvent accessible surface area, and mapping electrostatic potentials. These analyses deepen understanding of molecular interactions and enhance interpretation of simulation results.
hello Dear Chuck A Arize
Thank you for your complete answer
Thank you very much
Could you please guide me in the following ways? exprimental or Theorcal?
Especially the first one:
study biochemically of The inhibition mechanism
examining water dynamics,
identifying allosteric sites,
analyzing binding pathways,
and mapping electrostatic potentials