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Conformational Change
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change 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''. Factors that may induce such changes include temperature, pH, voltage, light in chromophores, concentration of ions, phosphorylation, or the binding of a ligand. 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. Laboratory analysis Many biophysical techniques such as crystallography, NMR, electron paramagnetic resonance (EPR) using spin label techniques, circular dichroism (CD), hydrogen exchange, and FRET can be used to study macromo ...
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Kinesin Walking
A kinesin is a protein complex belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzyme). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as Axonal transport#Anterograde transport, anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in Axonal transport#Retrograde transport, retrograde transport. Discovery The first kinesins to be discovered were microtubule-based anterograde intracellular trans ...
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Dual-polarization Interferometry
Dual-polarization interferometry (DPI) is an analytical technique that probes molecular layers adsorbed to the surface of a waveguide using the evanescent wave of a laser beam. It is used to measure the conformational change in proteins, or other biomolecules, as they function (referred to as the conformation activity relationship). Instrumentation DPI focuses laser light into two waveguides. One of these functions as the "sensing" waveguide having an exposed surface while the second one functions to maintain a reference beam. A two-dimensional interference pattern is formed in the far field by combining the light passing through the two waveguides. The DPI technique rotates the polarization of the laser, to alternately excite two polarization modes of the waveguides. Measurement of the interferogram for both polarizations allows both the refractive index and the thickness of the adsorbed layer to be calculated. The polarization can be switched rapidly, allowing real-time me ...
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Mechanoreceptor
A mechanoreceptor, also called mechanoceptor, is a sensory receptor that responds to mechanical pressure or distortion. Mechanoreceptors are located on sensory neurons that convert mechanical pressure into action potential, electrical signals that, in animals, are sent to the central nervous system. Vertebrate mechanoreceptors Cutaneous mechanoreceptors Cutaneous mechanoreceptors respond to mechanical stimuli that result from physical interaction, including pressure and vibration. They are located in the skin, like other cutaneous receptors. They are all innervated by Aβ fibers, except the mechanorecepting free nerve endings, which are innervated by A delta fiber, Aδ fibers. Cutaneous mechanoreceptors can be categorized by what kind of sensation they perceive, by the rate of adaptation, and by morphology. Furthermore, each has a different receptive field. By sensation * The Slowly Adapting type 1 (SA1) mechanoreceptor, with the Merkel corpuscle end-organ (also known as M ...
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Ion Channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiology), gating the flow of ions across the cell membrane, controlling the flow of ions across secretion, secretory and epithelial cells, and regulating cell (biology), cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophore, ionophoric proteins, the other being ion transporters. The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. Basic features There are two distinctive features of ion channels that differentiate them from other types of ion ...
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Protein Complexes
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple catalytic domains are found in a single polypeptide chain. Protein complexes are a form of quaternary structure. Proteins in a protein complex are linked by non-covalent protein–protein interactions. These complexes are a cornerstone of many (if not most) biological processes. The cell is seen to be composed of modular supramolecular complexes, each of which performs an independent, discrete biological function. Through proximity, the speed and selectivity of binding interactions between enzymatic complex and substrates can be vastly improved, leading to higher cellular efficiency. Many of the techniques used to enter cells and isolate proteins are inherently disruptive to such large complexes, complicating the task of determining the components of a complex. Examples of protein complexes include the ...
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Motor Proteins
Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They do this by converting chemical energy into mechanical work by the hydrolysis of ATP. Cellular functions Motor proteins are the driving force behind most active transport of proteins and vesicles in the cytoplasm. Kinesins and cytoplasmic dyneins play essential roles in intracellular transport such as axonal transport and in the formation of the spindle apparatus and the separation of the chromosomes during mitosis and meiosis. Axonemal dynein, found in cilia and flagella, is crucial to cell motility, for example in spermatozoa, and fluid transport, for example in trachea. The muscle protein myosin "motors" the contraction of muscle fibers in animals. Diseases associated with motor protein defects The importance of motor proteins in cells becomes evident when they fail to fulfill their function. For example, kinesin deficiencies have been identified as the cause for Ch ...
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ABC Transporter
The ABC transporters, ATP synthase (ATP)-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transporters belong to translocases. ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated AAA ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to provide the energy needed for the translocation of substrates across membranes, either for uptake or for export of the substrate. Most of the uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair. ABC transporters are considered to be an ABC superfamily based on the similarities of the sequence and organiz ...
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Molecular Dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the Motion (physics), physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamics (mechanics), dynamic "evolution" of the system. In the most common version, the trajectory, trajectories of atoms and molecules are determined by Numerical integration, numerically solving Newton's laws of motion, Newton's equations of motion for a system of interacting particles, where Force (physics), forces between the particles and their potential energy, potential energies are often calculated using interatomic potentials or molecular mechanics, molecular mechanical Force field (chemistry), force fields. The method is applied mostly in chemical physics, materials science, and biophysics. Because molecular systems typically consist of a vast number of particles, it is impossible to determine the properties of such complex systems analyt ...
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Gaussian Network Model
The Gaussian network model (GNM) is a representation of a biological macromolecule as an elastic mass-and-spring (device), spring network to study, understand, and characterize the mechanical aspects of its long-time large-scale dynamics (mechanics), dynamics. The model has a wide range of applications from small proteins such as enzymes composed of a single protein domain, domain, to large Macromolecular Assembly, macromolecular assemblies such as a ribosome or a viral capsid. Protein domain dynamics plays key roles in a multitude of molecular recognition and cell signalling processes. Protein domains, connected by intrinsically disordered flexible linker domains, induce long-range allostery via Protein dynamics#Global flexibility: multiple domains, protein domain dynamics. The resultant dynamic modes cannot be generally predicted from static structures of either the entire protein or individual domains. The Gaussian network model is a minimalist, coarse-grained approach to stud ...
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Modal Analysis
Modal analysis is the study of the dynamic properties of systems in the frequency domain. It consists of mechanically exciting a studied component in such a way to target the Normal mode, modeshapes of the structure, and recording the vibration data with a network of sensors. Examples would include measuring the vibration of a car's body when it is attached to a shaker (testing device), shaker, or the White noise, noise pattern in a room when excited by a loudspeaker. Modern day experimental modal analysis systems are composed of 1) sensors such as transducers (typically accelerometers, load cells), or non contact via a Laser vibrometer, or Photogrammetry, stereophotogrammetric cameras 2) data acquisition system and an analog-to-digital converter front end (to digitize Analog signal, analog instrumentation signals) and 3) host PC (personal computer) to view the data and analyze it. Classically this was done with a SIMO (single-input, multiple-output) approach, that is, one excit ...
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X-ray Crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring the angles and intensities of the X-ray diffraction, a crystallography, crystallographer can produce a three-dimensional picture of the density of electrons within the crystal and the positions of the atoms, as well as their chemical bonds, crystallographic disorder, and other information. X-ray crystallography has been fundamental in the development of many scientific fields. In its first decades of use, this method determined the size of atoms, the lengths and types of chemical bonds, and the atomic-scale differences between various materials, especially minerals and alloys. The method has also revealed the structure and function of many biological molecules, including vitamins, drugs, proteins and nucleic acids such as DNA. X-ray crystall ...
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Fluorescence
Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colored visible light. The color of the light emitted depends on the chemical composition of the substance. Fluorescent materials generally cease to glow nearly immediately when the radiation source stops. This distinguishes them from the other type of light emission, phosphorescence. Phosphorescent materials continue to emit light for some time after the radiation stops. This difference in duration is a result of quantum spin effects. Fluorescence occurs when a photon from incoming radiation is absorbed by a molecule, exciting it to a higher energy level, followed by the emission of light as the molecule returns to a lower energy state. The emitted light may have a longer wavelength and, therefore, a lower photon energy than the absorbed radi ...
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