What is a good value for ligand efficiency?
|Parameter||Definition||Recommended range for fragment hits|
|Ligand efficiency||LE = −ΔDG/HA||LE ≥ 0.3|
|Fit quality||FQ = LE/LE_Scale||FQ ≥ 0.8|
|Ligand-lipophilicity efficiency||LLE = pIC50 − log P||LLE ≥ 3|
How do you calculate ligand efficiency?
A common method of calculating ligand efficiency (LE) is to divide the Gibbs free energy of binding (ΔG) by the number of heavy atoms (N) as: LE = (ΔG)/N.
Why is ligand efficiency important?
Ligand efficiency is used in drug discovery research programs to assist in narrowing focus to lead compounds with optimal combinations of physicochemical properties and pharmacological properties.
What is pKi in drug discovery?
The design of ligands binding efficiently to multiple targets is thus emerging as a new paradigm in drug discovery [10,11]. Accordingly, an alternative definition was subsequently proposed as the binding affinity (% inhibition or pKi) per MW unit .
What are ligand efficiency metrics?
Ligand efficiency metrics, which are measures of the in vitro biological activity corrected for the physicochemical property ‘load’ of the molecule, quantify how effectively the molecule uses its structural features in binding to the target.
What is ligand efficiency in Autodock?
Ligand efficiency is binding energy per atom of ligand to protein. Total energy is the sum of changes of all energetic terms included in scoring function of lingand or protein upon binding, plus the changes upon binding of the entropic terms. Torsion energy is related to dihedral term of internal energy.
What is PKI chemistry?
The reaction rate of a chemical reaction is determined by the rate of the slowest individual step (elementary reaction), called the rate-determining step. The activation energy of the rate-determining step is the highest of all individual steps of the chemical reaction.
What do PKI values mean?
As pKi is on the logarithmic scale, a one unit change in pKi represents an order of magnitude change in Ki. Medications with higher pKi (toward or greater than 9) having higher affinities and vice versa.
What is ligand efficiency in drug discovery?
Ligand efficiency measures quantify the molecular properties, particularly size and lipophilicity, of small molecules that are required to gain binding affinity to a drug target. The application of ligand efficiency metrics has been widely reported in the selection and optimization of fragments, hits and leads.
What is lipophilic ligand efficiency?
Lipophilic ligand efficiency (LLE, equation 4) is simply the difference between p(Activity) and lipophilicity (cLogP or LogD) and is an estimate of the specificity of a molecule in binding to the target relative to partitioning into 1-octanol7.
What is a ligand and how is it used?
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein.