I aim to calculate free energy of substrate binding to my target protein, that contain Mg2+ ions at the active site cavity. Furthermore, I wish to analyse changes in binding energy ladscapes upon local point mutations. Which program is more suited for asessment of binding energies of proteins containing metal ions in their active site? Your suggestions are much appreciated.
Hi Raj,
For calculating binding energy of small molecules (ligands) you can use freely available software like AutoDock. But for that, you must have crystal structure of protein in presence of Metal ions in the active site, which you are proposing. Also by point mutation of known residue into desired another residue, you can study calculate the binding energy of molecule to receptor in presence of Metal ions.
For large molecules (coenzymes, peptides, substrates having large size), due to flexibility constraint of AutoDock, you might have to explore and use another tools like Glide (large molecules, small peptides), Haddock ( large peptides, proteins) for straightforward calculation of docking free energy.
For electronic level calculation, and effect of Metal ions on substrate binding in active site, you have to use QM/MM approach.
regards
Tanuj
You can try to mmpbsa which could give an idea about real life binding mode (partially). This could be done with either Amber or Gromacs.
Molecular dynamics simulations using Q molecular dynamics software package: free energy perturbation (FEP), linear interaction energy (LIE). "Point charge" and "dummy atom" models of metal ions can be defined.
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Q: http://xray.bmc.uu.se/~aqwww/q/
Hi Raj Kumar
Is there a particular free energy calculation method adapted for metalloproteins?
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