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What is a good ligand efficiency value?

What is a good ligand efficiency value?

F Ligand Efficiency It is helpful, particularly when trying to assess the relative value of fragments for follow-up in fragment-based drug design [53]. To obtain a final compound with MW <500 and ≈10 nM potency, LE needs to stay above 1.25 kJ/mol per HA [48].

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.

How do you calculate ligand efficiency?

Ligand efficiency (LE) is most commonly defined as the ratio of the affinity of a ligand divided by the number of heavy (nonhydrogen) atoms in the molecule (LE = ∆G/[number of heavy atoms]).

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 Glide ligand efficiency?

Ligand efficiency is a measurement of the binding energy per atom of a ligand to its binding partner, such as a receptor or enzyme. Mathematically, ligand efficiency (LE) can be defined as the ratio of Gibbs free energy (ΔG) to the number of non-hydrogen atoms of the compound: LE = (ΔG)/N.

What is nature of ligand?

In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central atom to form a coordination complex. The nature of metal–ligand bonding can range from covalent to ionic. Furthermore, the metal–ligand bond order can range from one to three.

What is a good ligand?

Lewis bases are ligands with lesser electronegativity; hence will they will be stronger. Therefore, oxygen or halogen donors are weak field ligands and the ones in which nitrogen or carbon atom is the donor are strong field ligands.

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.

Which ligand is the strongest?

According to this series $CO$ is the strongest ligand among the following because carbon is donor in this, it has double bond $(C = O)$ and is positively charged. Note: The strength of any ligand is determined by the amount of crystal field energy (CFT).

Which is the best value for ligand efficiency?

Nevertheless, independent of how the scaling function is derived, FQ values near one indicate near optimal ligand binding. LE and corresponding FQ are useful for optimizing affinity with respect to molecular size. However, to achieve optimal ADMET properties molecular size and lipophilicity are important factors to consider.

How does LLE affect the affinity of a ligand?

High LLE favours compounds that gain a lot of their affinity through directed interactions thus making the interaction with the receptor more specific. While one can say that LLE describes how efficient a ligand exploits its lipophilicity, no explicit measure of molecular size is used.

Is the ligand efficiency metric a physical metric?

Consequently, perception of efficiency varies with the choice of concentration unit and it is argued that the ligand efficiency metric is not physically meaningful nor should it be considered to be a metric.

Can a ligand be evaluated independent of size?

The authors conclude that LE cannot be evaluated independent of the molecular size. To enable a size-independent comparison of ligands they derived a scaling function (LE_Scale) by fitting an exponential function to the maximal ligand efficiency values observed for a given HA count.