Structure-activity relationship
Encyclopedia
The structure–activity relationship (SAR) is the relationship between the chemical
or 3D structure of a molecule and its biological activity
. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism. This allows modification of the effect or the potency
of a bioactive compound (typically a drug) by changing its chemical structure
. Medicinal chemists
use the techniques of chemical synthesis
to insert new chemical groups into the biomedical compound and test the modifications for their biological effects.
This method was refined to build mathematical relationships between the chemical structure and the biological activity, known as quantitative structure–activity relationships (QSAR). A related term is structure affinity relationship (SAFIR).
ability, biotransformation
ability, solubility
, target activity, and so on, might depend on another difference. A good example was given in the bioisosterism review of Patanie/LaVoie.
In general, one is more interested in finding strong trends
. Created hypotheses usually rely on a finite number of chemical data. Thus, the induction principle should be respected to avoid overfitted
hypotheses and deriving overfitted and useless interpretations on structural/molecular data.
The SAR paradox refers to the fact that it is not the case that all similar molecules have similar activities.
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
or 3D structure of a molecule and its biological activity
Biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or pharmacophore but can be modified by the other...
. The analysis of SAR enables the determination of the chemical groups responsible for evoking a target biological effect in the organism. This allows modification of the effect or the potency
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
of a bioactive compound (typically a drug) by changing its chemical structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
. Medicinal chemists
Medicinal chemistry
Medicinal chemistry and pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where it is involved with design, chemical synthesis and development for market of pharmaceutical...
use the techniques of chemical synthesis
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
to insert new chemical groups into the biomedical compound and test the modifications for their biological effects.
This method was refined to build mathematical relationships between the chemical structure and the biological activity, known as quantitative structure–activity relationships (QSAR). A related term is structure affinity relationship (SAFIR).
SAR and SAR paradox
The basic assumption for all molecule-based hypotheses is that similar molecules have similar activities. This principle is the basis of a SAR. The underlying problem is therefore how to define a small difference on a molecular level, since each kind of activity, e.g. reactionChemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
ability, biotransformation
Biotransformation
Biotransformation is the chemical modification made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation....
ability, solubility
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
, target activity, and so on, might depend on another difference. A good example was given in the bioisosterism review of Patanie/LaVoie.
In general, one is more interested in finding strong trends
Trend estimation
Trend estimation is a statistical technique to aid interpretation of data. When a series of measurements of a process are treated as a time series, trend estimation can be used to make and justify statements about tendencies in the data...
. Created hypotheses usually rely on a finite number of chemical data. Thus, the induction principle should be respected to avoid overfitted
Overfitting
In statistics, overfitting occurs when a statistical model describes random error or noise instead of the underlying relationship. Overfitting generally occurs when a model is excessively complex, such as having too many parameters relative to the number of observations...
hypotheses and deriving overfitted and useless interpretations on structural/molecular data.
The SAR paradox refers to the fact that it is not the case that all similar molecules have similar activities.
See also
- Combinatorial chemistryCombinatorial chemistryCombinatorial chemistry involves the rapid synthesis or the computer simulation of a large number of different but structurally related molecules or materials...
- Congener
- Conformation activity relationshipConformation activity relationshipConformation-activity relationship is the relationship between the biological activity and the conformation or conformational changes of a biomolecule...