In silico methods became widely used in the fields of structural molecular biology and structure-based drug design with the rapid increase in computational power. Molecular docking [2–4] is one of these in silico techniques. Docking is a method which predicts preferred orientation (on the basis of binding energy) of one molecule to the second to form a stable complex. In the field of drug design, first molecule is usually protein/enzyme/DNA and the second one is small organic molecule/small peptides as potential drug candidate. Knowledge of preferred orientation of ligand and protein used to predict binding affinity and to discriminate high-affinity drug candidates from the low-affinity compounds. 2.6.1Lock and key analogy Molecular docking is sometimes described as a problem of lock and key, where one is interested in finding the correct orientation of a key (ligand) that will open the lock (protein). Although this analogy is simple to understand but it does not account for inherent flexibility of proteins and ligands which is why more appropriate term hand-in-glove is used sometimes. 2.6.2 Rigid-body docking vs. flexible docking The docking problem involves many degrees of freedom [18]. There are three translational and three rotational degrees of freedom for each molecule as well as the conformational degrees of freedom for both molecules. The simplest approach to docking is to take into account only translational and rotational degrees of freedom and treat both receptor and ligand as rigid objects. This approach is known as rigid-body docking [18]. It depends from case to case, whether this approximation is accurate enough or not. If there are significant conformational changes within the molecules during the complex formation... ... middle of paper ... ...us contributions to the binding free energy. An equation of this kind would have the following contributions: ΔGbind = ΔGsolvent +ΔGconf +ΔGint +ΔGrot +ΔGt/r +ΔGvib (2.1) ΔGsolvent represents contributions of solvent effects, which arise from the interaction of the solvent and ligand, receptor and the intermolecular complex. ΔGconf arises from the conformational changes in both protein and especially more flexible ligand. ΔGint stands for the free energy of specific protein-ligand interactions._Grot is the free energy loss caused by freezing of the internal rotations. ΔGr/t is a change in rotational and translational free energy due to association of receptor and ligand, forming a single body and ΔGvib corresponds to free energy changes in vibrational modes. More details on each term can be found for example in [18] or [28].
11C → 11B + e+ + ν Energy given off as a result e + 0.96 MeV
Receptor tyrosine kinase is a cell membrane receptor system that can trigger multiple cellular responses simultaneously. It requires two receptor tyrosine kinase proteins, which are initially individual polypeptides that each have a signal-binding site, an α helix spanning the cell membrane, and a tail of multiple tyrosines. When signal molecules bind to both proteins they attach through a process called dimerization, forming a dimer. This process activates, or phosphorylates, the ends of the tyrosines, also known as tyrosine-kinase regions. Once the dimer is activated, multiple inactive relay proteins are able to bind to the tyrosine-kinase regions. Each of these proteins trigger a cellul...
...s to interfere with bonding to the receptors. The final possibility uses CNP, which downregulates the activation in MAP kinase pathways in the chondrocytes (4).
The symbiosis of the symbiosis. That means by the interaction between the side-chains of the enzyme and the atoms of the substrate, the enzyme can encourage the formation or breaking of bonds in a substrate molecule. Each enzyme possesses an active site. The active site is a region of enzyme which allows a substrate to bind to it. The configuration of the active site gives the specificity of the enzyme.
The structures of liposomes are spherical and are usually between 15nm and 1000 nm in diameter. They are able to target the ligands that are attached to their surface to direct them to the appropriate sites wi...
type of energy is lost or gained, and whether or not a factor that is
Enzymes have the ability to act on a small group of chemically similar substances. Enzymes are very specific, in the sense that each enzyme is limited to interact with only one set of reactants; the reactants are referred to as substrates. Substrates of an enzyme are the chemicals altered by enzyme-catalysed reactions. The extreme specific nature of enzymes are because of the complicated three-dimensional shape, which is due to the particular way the amino acid chain of proteins folds.
...degree of intermolecular association. By adjusting the formulation or the chemical moieties of the drug delivery system, the moment and the location of the release of the drug may be controlled (You e.a. 2010).
energy was given out or taken in. We can show this on a graph. Alcohol
Non – competitive inhibitors change the globular shape of an enzyme so that a enzyme-substrate complexes can’t form meaning a lower optimum rate of reaction. Enzymes in Medicine = == ==
For example, some of the proteins contain pleckstrin homology domains that bind phosphoinositide and others contain C2 domains that bind membrane lipids in the presence of Ca2+, some proteins contain positively charged regions that bind to negatively charged phosphoglycerides and others contain covalently attached fatty acyl groups or prenyl groups that anchor them to membranes. Another example is Annexin shows Ca2+ dependent binding to the cytosolic surfaces of cell membranes. Ca2+ ions bind to the iface of each annexin and this promote protein–lipid interactions through a combination of electrostatic and hydrophobic mechanisms. The same result has been shown by crystallographic studies with phosphoglyceride analogs, suggested that some of the bound Ca2+ ions may bind directly to the oxygens of phospholipid head groups. Addition to this, adjacent membrane lipids that do not bind proteins directly may modulate the protein–lipid interactions, the binding of proteins to membrane surfaces may promote further changes in the structure and function of the proteins, and groups of proteins that bind to the same membrane surface may interact with each other to produce complex membrane
Enzymes are essential biological catalysts in the human body that biochemical reaction. Catalysts work by lowering the activation energy, the minimum energy required for a reaction to occur, which increases the rate of the reaction (Burdge, 2014). Enzymes catalyze reactions by applying pressure onto the bonds of the substrate which lowers the activation energy and breaks these bonds to form products. Even though some enzymes have been found to be non-proteins, most of them are globular proteins which possess an active site where the substrate attaches itself (Raven, 114). The two models that describe the manner in which substrates attach to enzymes are the lock-and-key model and the induced fit model. The lock-and-key model is used to explain an enzyme that fits to only one type of substrate. It is like a lock and key in the sense that only one lock can fit into a key, therefore, only one substrate can fit into the active site of an enzyme that follows this model. On the other hand, an enzyme that follows the induced fit model slightly changes its shape in order for the substrate to...
I have always been fascinated by Biology and Computer Science which propelled me to take up my undergraduate studies in the field of Bioinformatics. As a part of my undergraduate curriculum, I have been exposed to a variety of subjects such as “Introduction to Algorithms”, “System Biology”, “PERL for Bioinformatics”, “Python”, “Structure and Molecular Modeling” and “Genomics and Proteomics” which had invoked my interest in areas such as docking algorithms, protein structure prediction, practical aspects of setting and running simulation, gene expression prediction through computational analysis. These fields have both a strong computational flavour as well as the potential for research which is what attracts me towards them.
More than 45 million chemical compounds are known and the number may increase in million every year, without cheminformatics, the access of these huge amounts of information is very difficult.
Molecular pharmacology deals with the biochemical and biophysical characteristics of interactions between molecules of different substances and those of the cell. In other words, it is molecular biology applied to pharmacologic and toxicologic questions. The methods of molecular pharmacology include precise mathematical, physical, chemical and molecular biological techniques to understand how cells respond to hormones or pharmacologic agents, and how chemical structure correlates with biological activity of various