Conformation activity relationship
Encyclopedia
Conformation-activity relationship is the relationship between the biological activity
and the conformation
or conformational change
s of a biomolecule. This terminology emphasizes the importance of dynamic conformational changes for the biological function, rather than the importance of static three-dimensional structure used in the analysis of structure activity relationships.
The conformational changes usually take place during intermolecular association
, such as protein–protein interaction or protein-ligand binding. A binding partner changes the conformation of a biomolecule (e.g. a protein) to enable or disable its biochemical activity.
Methods for analysis of conformation activity relationship vary from in silico
or using experimental methods such as X-ray crystallography
and NMR
where the conformation before and after activity can be compared statically or using dynamic methods such as dual polarisation interferometry
or circular dichroism
where the kinetics
as well as degree of conformational change can be quantified.
Dynamic
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...
and the conformation
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 conformational change
Conformational change
A macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
s of a biomolecule. This terminology emphasizes the importance of dynamic conformational changes for the biological function, rather than the importance of static three-dimensional structure used in the analysis of structure activity relationships.
The conformational changes usually take place during intermolecular association
Binding (molecular)
Molecular binding is an attractive interaction between two molecules which results in a stable association in which the molecules are in close proximity to each other...
, such as protein–protein interaction or protein-ligand binding. A binding partner changes the conformation of a biomolecule (e.g. a protein) to enable or disable its biochemical activity.
Methods for analysis of conformation activity relationship vary from in silico
In silico
In silico is an expression used to mean "performed on computer or via computer simulation." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo and in vitro which are commonly used in biology and refer to experiments done in living organisms and outside of living organisms,...
or using experimental methods such as X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
and NMR
NMR
NMR may refer to:Applications of Nuclear Magnetic Resonance:* Nuclear magnetic resonance* NMR spectroscopy* Solid-state nuclear magnetic resonance* Protein nuclear magnetic resonance spectroscopy* Proton NMR* Carbon-13 NMR...
where the conformation before and after activity can be compared statically or using dynamic methods such as dual polarisation interferometry
Dual Polarisation Interferometry
Dual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...
or circular dichroism
Circular dichroism
Circular dichroism refers to the differential absorption of left and right circularly polarized light. This phenomenon was discovered by Jean-Baptiste Biot, Augustin Fresnel, and Aimé Cotton in the first half of the 19th century. It is exhibited in the absorption bands of optically active chiral...
where the kinetics
Chemical kinetics
Chemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...
as well as degree of conformational change can be quantified.
Experimental techniques
Static- X-ray crystallographyX-ray crystallographyX-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
- NMRNMRNMR may refer to:Applications of Nuclear Magnetic Resonance:* Nuclear magnetic resonance* NMR spectroscopy* Solid-state nuclear magnetic resonance* Protein nuclear magnetic resonance spectroscopy* Proton NMR* Carbon-13 NMR...
Dynamic
- Dual polarisation interferometryDual Polarisation InterferometryDual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...
- Circular DichroismCircular dichroismCircular dichroism refers to the differential absorption of left and right circularly polarized light. This phenomenon was discovered by Jean-Baptiste Biot, Augustin Fresnel, and Aimé Cotton in the first half of the 19th century. It is exhibited in the absorption bands of optically active chiral...