Conformational isomerismIn chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds (refer to figure on single bond rotation). While any two arrangements of atoms in a molecule that differ by rotation about single bonds can be referred to as different conformations, conformations that correspond to local minima on the potential energy surface are specifically called conformational isomers or conformers.
LigandIn coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electron pairs, often through Lewis bases. The nature of metal–ligand bonding can range from covalent to ionic. Furthermore, the metal–ligand bond order can range from one to three. Ligands are viewed as Lewis bases, although rare cases are known to involve Lewis acidic "ligands".
Ligand (biochemistry)In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix.
Allosteric regulationIn biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the allosteric site or regulatory site. Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change and/or a change in protein dynamics. Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors.
Drug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery, as with penicillin. More recently, chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that had a desirable therapeutic effect in a process known as classical pharmacology.
Binding siteIn biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may include other proteins (resulting in a protein-protein interaction), enzyme substrates, second messengers, hormones, or allosteric modulators. The binding event is often, but not always, accompanied by a conformational change that alters the protein's function.
Eclipsed conformationIn chemistry an eclipsed conformation is a conformation in which two substituents X and Y on adjacent atoms A, B are in closest proximity, implying that the torsion angle X–A–B–Y is 0°. Such a conformation can exist in any open chain, single chemical bond connecting two sp3-hybridised atoms, and it is normally a conformational energy maximum. This maximum is often explained by steric hindrance, but its origins sometimes actually lie in hyperconjugation (as when the eclipsing interaction is of two hydrogen atoms).
Drug designDrug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Zinc fingerA zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. It was originally coined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (Xenopus laevis) transcription factor IIIA. However, it has been found to encompass a wide variety of differing protein structures in eukaryotic cells.
Staggered conformationIn organic chemistry, a staggered conformation is a chemical conformation of an ethane-like moiety abcX–Ydef in which the substituents a, b, and c are at the maximum distance from d, e, and f; this requires the torsion angles to be 60°. It is the opposite of an eclipsed conformation, in which those substituents are as close to each other as possible. Such a conformation exists in any open chain single chemical bond connecting two sp3-hybridised atoms, and is normally a conformational energy minimum.
Fragment-based lead discoveryFragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. Fragments are small organic molecules which are small in size and low in molecular weight. It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity. FBLD can be compared with high-throughput screening (HTS).
Intrinsically disordered proteinsIn molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs range from fully unstructured to partially structured and include random coil, molten globule-like aggregates, or flexible linkers in large multi-domain proteins. They are sometimes considered as a separate class of proteins along with globular, fibrous and membrane proteins.
Hydrogen bondIn chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a lone pair of electrons—the hydrogen bond acceptor (Ac). Such an interacting system is generally denoted , where the solid line denotes a polar covalent bond, and the dotted or dashed line indicates the hydrogen bond.
Bridging ligandIn coordination chemistry, a bridging ligand is a ligand that connects two or more atoms, usually metal ions. The ligand may be atomic or polyatomic. Virtually all complex organic compounds can serve as bridging ligands, so the term is usually restricted to small ligands such as pseudohalides or to ligands that are specifically designed to link two metals. In naming a complex wherein a single atom bridges two metals, the bridging ligand is preceded by the Greek letter mu, μ, with a subscript number denoting the number of metals bound to the bridging ligand.
Protein dynamicsProteins are generally thought to adopt unique structures determined by their amino acid sequences. However, proteins are not strictly static objects, but rather populate ensembles of (sometimes similar) conformations. Transitions between these states occur on a variety of length scales (tenths of Å to nm) and time scales (ns to s), and have been linked to functionally relevant phenomena such as allosteric signaling and enzyme catalysis.
Receptor antagonistA receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins. They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors.
X-ray crystallographyX-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal. From this electron density, the mean positions of the atoms in the crystal can be determined, as well as their chemical bonds, their crystallographic disorder, and various other information.
A valueA-values are numerical values used in the determination of the most stable orientation of atoms in a molecule (conformational analysis), as well as a general representation of steric bulk. A-values are derived from energy measurements of the different cyclohexane conformations of a monosubstituted cyclohexane chemical. Substituents on a cyclohexane ring prefer to reside in the equatorial position to the axial.
Ligand binding assayA ligand binding assay (LBA) is an assay, or an analytic procedure, which relies on the binding of ligand molecules to receptors, antibodies or other macromolecules. A detection method is used to determine the presence and extent of the ligand-receptor complexes formed, and this is usually determined electrochemically or through a fluorescence detection method. This type of analytic test can be used to test for the presence of target molecules in a sample that are known to bind to the receptor.
Allosteric modulatorIn pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcoholic beverages, function as psychoactive drugs. The site that an allosteric modulator binds to (i.e., an allosteric site) is not the same one to which an endogenous agonist of the receptor would bind (i.e., an orthosteric site). Modulators and agonists can both be called receptor ligands.
