Can I explain the kinetics of a ligand binding to a target protein (association and dissociation rates) by looking at the protein-ligand co-structure?

Editing my question after a few comments: I have a set of ligands targeting the same protein. These ligands show different kinetics properties, i.e. different association and dissociation rates. Would it be possible to explain why they have a different kinetics if I had the x-ray structure of the different protein-ligand complexes? Would I be able to say that ligand A has a slower dissociation time compared to ligand B because it makes for example 3 H-bonds instead of 2? How accurate would this conclusion be? Would I need in any case MD simulations?

  • $\begingroup$ Theoretically, structure defines function. However, it is very complicated. When people design enzyme on paper and then synthesize it, predictions are rarely accurate. $\endgroup$ – aaaaaa Jul 8 '15 at 21:55
  • $\begingroup$ I am not sure what you want to know exactly. $\endgroup$ – 243 Jul 8 '15 at 22:27
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    $\begingroup$ It is not generally possible to have an idea about dynamic properties from static data. I guess you can use molecular dynamics simulation based on the structural data to have some idea about kinetics (I am no expert in this area). $\endgroup$ – WYSIWYG Jul 9 '15 at 4:26
  • $\begingroup$ yes you probably need some molecular dynamics simulations. And what about if I have several co-structures with the same protein but with different ligands with different kinetic properties? Can I explain their different kinetics based on their binding mode? $\endgroup$ – metionina Jul 9 '15 at 10:06
  • $\begingroup$ Specifically what data do you have? Do you have a docked crystal structure? $\endgroup$ – James Jul 10 '15 at 1:09

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