Draft:Quantitative Estimation of Druglikeness
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Quantitative Estimation of Druglikeness (QED) is a metric used in cheminformatics to quantify the "drug-likeness" of a molecule. Druglikeness referiss to the likelihood that a small molecule possesses favorable properties that make it suitable for development as a drug. QED combines multiple molecular descriptors into a single score to provide a measure of drug-likeness.
Properties considered
[edit]QED integrates a variety of molecular properties that are known to influence a molecule's suitability as a drug candidate, including:
- Molecular weight (MW): Molecules with very high or very low molecular weight may not exhibit favorable pharmacokinetics.
- Lipophilicity (logP): LogP measures the balance between a molecule's solubility in water and fat, which affects its ability to traverse cell membranes.
- Hydrogen bond donors (HBD) and acceptors (HBA): These properties are important for the molecule's interactions with biological targets.
- Number of rotatable bonds: Molecules with fewer rotatable bonds are often more rigid and may fit better into binding sites.
- Aromatic rings: The presence of aromatic rings is often associated with favorable drug properties.
- Structural alerts: These are chemical substructures that are associated with toxicity or other undesirable properties.
Each property is transformed into a desirability function that returns a value between 0 and 1, with higher values indicating a more favorable drug-likeness profile. These individual scores are combined to calculate the overall QED score.
Calculation of QED
[edit]QED is calculated by multiplying the individual desirability scores for each property, resulting in a final score between 0 and 1. A QED score of 1 indicates an ideal drug-like molecule, while a score closer to 0 suggests the molecule is less likely to possess favorable drug-like characteristics.
The calculation can be expressed as:
where D() represents the desirability function for each molecular property.
Applications in drug discovery
[edit]QED is a useful tool in early-stage drug discovery for screening large compound libraries and prioritizing molecules with higher QED scores for further development. It is also employed to guide lead optimization by helping chemists identify structural modifications that improve a molecule's drug-likeness.
- Compound screening: Researchers can quickly assess the drug-likeness of many compounds and focus on those with high QED scores.
- Lead optimization: During the optimization phase of drug development, QED helps in evaluating how structural changes impact the overall drug-likeness of a molecule.
QED is often used in conjunction with other drug-likeness rules, such as Lipinski's Rule of Five, but provides a more quantitative assessment by considering multiple factors simultaneously.
Use in software
[edit]QED is commonly implemented in cheminformatics software, including the open-source toolkit ''RDKit'', which provides functions for computing QED from a molecule's structure, typically represented by a SMILES string.
See also
[edit]References
[edit]Further reading
[edit]- Bickerton, G. R., Paolini, G. V., Besnard, J., Muresan, S., & Hopkins, A. L. (2012). "Quantifying the chemical beauty of drugs". Nature Chemistry. (https://doi.org/10.1038/nchem.1243).
External links
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