As far as I know,
1. Binding free energy is the sum of all the intermolecular interactions that is present between the ligand and the target.
2. Docking Score is the scoring function used to predict the binding affinity of both ligand and target once it is docked.
3. Binding Affinity is another term used to find the efficiency of ligand-target complex by scoring the interactions present between the complex through scoring functions, force field as well as statistical methods.
The tools such as :
- Discovery Studio gives interaction energy and docking energy,
- Autodock Vina gives Binding Energy
- MOE gives Docking Score, Energy of conformed and restoring scores.
- Glide gives Binding free energy, Docking Score and Binding affinity separately.
Can anyone tell me the difference between the above-mentioned terms? Also, can you suggest a good software/ tool other that Glide, to find these 3 terms separately?
Binding Affinity is the equilibrium constant of complex formation, laws of thermodynamics relate it to the change in Gibbs free energy upon binding:
The change in Gibbs free Energy of Binding is equal to - RT times the natural logarithm of the Equilibrium constant, where R is the gas constant and T the absolute temperature. https://en.wikipedia.org/wiki/Gibbs_free_energy.
These are experimentally determinable parameters that you wish to predict by your calculation.
The Docking score is a computational result that is specific for a particular program and energy function, and that in an ideal case allows you to predict binding free energy and binding affinity, or to at least rank different complexes according to those parameters.
Samee Ullah, it is possible to estimate binding affinity computationally, by running two sets of MD simulations: (i) protein-ligand complex in water and (ii) free ligand in water.
For the ligand, anything that surrounds it is a solvent, be it a water molecule or an amino acid residue of the protein; protein-ligand binding is a solvent-substitution process.
Samee Ullah , linear interaction energy (LIE), linear response approximation (LRA), and free energy perturbation (FEP) are mature methods: they have been around for more than 20 (LIE and LRA) and more than 60 years (FEP).
Entropy is included implicitly in the ensemble of configurations obtained from sampling the conformational space in molecular dynamics simulations. There is no need to simulate free protein in water, or free water in water, or both, to obtain protein-ligand binding free energy; nor is there a need to simulate the actual process of binding or unbinding of the ligand.
As for the LIE parameters alpha and beta, no, they are not freely adjustable fudge factors; the original and refined alpha and beta are robust enough and work well not only for proteins but also for nucleic acids; and not only that, the scaled van der Waals and electrostatic interaction energies are physically meaningful and account for all contributions to the protein-ligand binding free energy.
The only limitation is force field (but systematic errors tend to cancel out in relative free energies) and sampling (true convergence is impossible, 1 to 2 kcal/mol is the lower limit of uncertainty).
It is certainly not true that none of the above-mentioned methods have not been used to predict protein-ligand binding free energies.
And it is certainly not true that the use of these methods requires the knowledge of the ligand binding mode; in fact, these methods can be used to discriminate between alternative binding modes, for example those obtained from molecular docking.
Samee Ullah so what you call result from docking autock? is it docking score only and to call it BFE or binding affinity, i should do more?
@Sameen Ullah The binding affinity can be further studied or evaluated by MD simulations as well as using MM-PBSA/GBSA analysis right?
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