Protein ligands
Encyclopedia
In biochemistry
, a protein
ligand
is an atom
, a molecule
or an ion
which can bind to a specific site (the binding site
) on a protein. Alternative names used to mean a protein ligand are affinity reagents or protein binders. To date, antibodies are the most widely used protein ligands in life-science investigations, however, other molecules such as protein scaffolds
, nucleic acids, peptides are also being used.
Main methods to study protein–ligand interactions are principal hydrodynamic and calorimetric techniques, and principal spectroscopic and structural methods such as
Other techniques include:
fluorescence intensity,
bimolecular fluorescence complementation,
FRET (fluorescent resonance energy transfer) / FRET quenching
surface plasmon resonance,
Bio-Layer Interferometry
,
Coimmunopreciptation
indirect ELIS,
equilibrium dialysis,
gel electrophoresis,
far western blot,
fluorescence polarization anisotropy,
electron paramagnetic resonance,
Microscale Thermophoresis
The dramatically increased computing power of supercomputers and personal computers has made it possible to study protein–ligand interactions also by means of computational chemistry
. For example, a worldwide grid of well over a million ordinary PCs was harnessed for cancer research in the project grid.org
, which ended in April 2007. Grid.org has been succeeded by similar projects such as World Community Grid
, Human Proteome Folding Project
, Compute Against Cancer
and Folding@Home
.
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
is an atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
, a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
or an ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
which can bind to a specific site (the binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
) on a protein. Alternative names used to mean a protein ligand are affinity reagents or protein binders. To date, antibodies are the most widely used protein ligands in life-science investigations, however, other molecules such as protein scaffolds
Scaffold protein
In biology, scaffold proteins are crucial regulators of many key signaling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes...
, nucleic acids, peptides are also being used.
Main methods to study protein–ligand interactions are principal hydrodynamic and calorimetric techniques, and principal spectroscopic and structural methods such as
- Fourier transform spectroscopyFourier transform spectroscopyFourier transform spectroscopy is a measurement technique whereby spectra are collected based on measurements of the coherence of a radiative source, using time-domain or space-domain measurements of the electromagnetic radiation or other type of radiation....
- Raman spectroscopyRaman spectroscopyRaman spectroscopy is a spectroscopic technique used to study vibrational, rotational, and other low-frequency modes in a system.It relies on inelastic scattering, or Raman scattering, of monochromatic light, usually from a laser in the visible, near infrared, or near ultraviolet range...
- Fluorescence spectroscopyFluorescence spectroscopyFluorescence spectroscopy aka fluorometry or spectrofluorometry, is a type of electromagnetic spectroscopy which analyzes fluorescence from a sample. It involves using a beam of light, usually ultraviolet light, that excites the electrons in molecules of certain compounds and causes them to emit...
- 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...
- Nuclear magnetic resonanceNuclear magnetic resonanceNuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
- Mass spectrometryMass spectrometryMass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
- Atomic force microscopeAtomic force microscopeAtomic force microscopy or scanning force microscopy is a very high-resolution type of scanning probe microscopy, with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the optical diffraction limit...
- Paramagnetic probes
- 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...
Other techniques include:
fluorescence intensity,
bimolecular fluorescence complementation,
FRET (fluorescent resonance energy transfer) / FRET quenching
surface plasmon resonance,
Bio-Layer Interferometry
Bio-Layer Interferometry
Bio-Layer Interferometry is a label-free technology for measuring biomolecular interactions within the interactome. It is an optical analytical technique that analyzes the interference pattern of white light reflected from two surfaces: a layer of immobilized protein on the biosensor tip, and an...
,
Coimmunopreciptation
indirect ELIS,
equilibrium dialysis,
gel electrophoresis,
far western blot,
fluorescence polarization anisotropy,
electron paramagnetic resonance,
Microscale Thermophoresis
Microscale Thermophoresis
Microscale Thermophoresis is a technology for the analysis of biomolecules. Microscale Thermophoresis is the directed movement of particles in a microscopic temperature gradient...
The dramatically increased computing power of supercomputers and personal computers has made it possible to study protein–ligand interactions also by means of computational chemistry
Computational chemistry
Computational chemistry is a branch of chemistry that uses principles of computer science to assist in solving chemical problems. It uses the results of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids...
. For example, a worldwide grid of well over a million ordinary PCs was harnessed for cancer research in the project grid.org
Grid.org
grid.org was a website and online community established in 2001 that focuses on cluster computing and grid computing software for users. For the first 6 years of its history it operated several different volunteer computing projects that allowed members to donate their spare computer cycles to...
, which ended in April 2007. Grid.org has been succeeded by similar projects such as World Community Grid
World Community Grid
World Community Grid is an effort to create the world's largest public computing grid to tackle scientific research projects that benefit humanity...
, Human Proteome Folding Project
Human Proteome Folding Project
The Human Proteome Folding Project is a collaborative effort between New York University , the Institute for Systems Biology and the University of Washington , using the Rosetta software developed by the Rosetta Commons....
, Compute Against Cancer
Compute Against Cancer
Compute Against Cancer is an initiative of Parabon Computation, Inc. powered by the Global Grid Exchange. The program provides cancer researchers access to supercomputing capabilities through Parabon’s Frontier Grid Platform. The Compute Against Cancer initiative provides a means for donors to make...
and Folding@Home
Folding@home
Folding@home is a distributed computing project designed to use spare processing power on personal computers to perform simulations of disease-relevant protein folding and other molecular dynamics, and to improve on the methods of doing so...
.