Protein-ligand代写 All fundamental processes in living organisms are a result of molecular recognition which is essentially the process of interaction
PROTEIN-LIGAND INTERACTION (HIV PROTEASE INHIBITOR)Protein-ligand代写
All fundamental processes Protein-ligand代写
in living organisms are a result of molecular recognition which is essentially the process of interaction between biological macromolecules or different minute molecules with high specificity and affinity to form distinct complexes. Among these macromolecules are proteins which play important roles in physiological processes such as the maintenance of structural integrity of cells, maintenance of cell defenses, metabolism, catabolism, anabolism and enzymatic catalysis by binding themselves to other molecules (Fersht, 2010; Brozino et al. 2015). On the other hand, there are macromolecules called ligands which bind to proteins resulting in changes in the structure of that protein thereby modulating it’s biological processes (Fell and Bowden 2011). Gaining greater insight into protein-ligand interactions and binding is, therefore, important as it can help up develop better drugs and improve therapeutic practices.
Perhaps one of the most significant utilization of protein–ligand interaction is in the fight against HIV, a disease that has ravaged parts of the worlds for decades.
One of the widely used protease inhibitors/ligands to fight HIV-1 is Tipranavir which prevents the replication of the HIV by binding to the active site of the HIV-1 protease thereby by elucidating its biological and biochemical roles. For the HIV to replicate, it integrates itself into the host cell DNA in infected cells and gains the genetic information for a new HIV. Sequentially, the virus produces non-functional gag and gag–pol polyproteins which the HIV protease cleaves into integral functional proteins products. Protein-ligand代写
Protein inhibitors such as Tipranavir can interfere with the native protease enzyme by disabling its ability to cleave the new viral polyprotein into essential protein resulting in immature and non-infectious virions. This inhibition occurs when Tipranavir binds with the active site of the protease enzyme through strong hydrogen bonds preventing the action of the protease. For proteins and enzymes to bind to the enzyme, their shape must partially or precisely fit onto the surface of the active site on the enzyme in a lock-and-key model. Moreover, the shape of the inhibitor usually resembles the shape of the substrate. These kinds of reversible inhibitors sometimes bind with an active site through covalent bonds but mostly form due to electrostatic and Van der Waals forces whereby they are attracted to binding sites due to proximity (Ray 2000).
According to Johnson et al. Protein-ligand代写
and Proschel et al. (2002;2015), as organisms grow they constantly break down bonds and molecules at a cellular level in a process called metabolism which is a combination of all chemical reactions that take place within the organism.The processes include catabolism in which breaks down more complex molecules to simpler molecules and catabolism in which simpler molecules are built into more complex molecules. In catabolic pathways, energy is released as molecules get broken down while anabolic pathways require energy to create more complex molecules. Pavlovicz and Li (2015) indicate that these biochemical processes are sequential thus need proteins (enzymes) to catalyze their specific molecular substrates.
In a similar process of protease inhibition, cells regulate metabolic processes by inhibiting or activating enzymes. To regulate biochemical processes, inhibitor molecules (ligands) competitively bind the active site of an enzyme thereby preventing it from bonding with the substrate. The breakdown of carbohydrates into glucose to produces energy and the synthesis of glucose into more complex carbohydrate molecules are an example of catabolic and anabolic pathways respectively. Organisms’ immune systems produce antibodies (proteins) which specifically bind to active sites foreign molecules (antigens) on the surface of pathogens resulting in their deactivation or destruction (Ray 2000).
There could be severe repercussions to an organism if these protein-ligand interactions fail to occur. Protein-ligand代写
For example, if a person’s body fails to regulate blood glucose levels effectively through regulation of enzymes they will ultimately suffer from diabetes. Similarly, an individual who is unable to produce antibodies for countering antigens produced by pathogens will succumb to disease due to immunodeficiency (Storch andThumser 2010). Such conditions notwithstanding, there is hope for such people since it is possible to manipulate protein enzyme interaction artificially through genetic interference. This procedure involves isolation of DNA that encodes a particular enzyme of interest and then cloning them and combining them with different promoter sequences allowing them to undertake the expression of the new enzyme in the host cells. This process has been successful in creating dopamine-producing cells in the treatment of Parkinson’s disease.
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Protein Function. Available from: http://www.ncbi.nlm.nih.gov/books/NBK26911/
Pröschel, M., Detsch, R., Boccaccini, A. R., & Sonnewald, U. (2015). Engineering of Metabolic Pathways by Artificial Enzyme Channels. Frontiers in Bioengineering and Biotechnology, 3, 168. http://doi.org/10.3389/fbioe.2015.00168
Bronzino, J.D. & Peterson, D.R., 2015. The biomedical engineering handbook, Boca Raton, FL: CRC. Protein-ligand代写
Fell D. and Cornish-Bowden, A., 2011. Understanding the control of metabolism (Vol. 2). London: Portland Press.
Ray, G. T. (2000). Part one: modulation of protein-ligand interaction through synthetic bifunctional molecules and endogenous proteins; Part two: efforts towards elucidation of microtubule-derived signal transduction and the mechanism of taxol. Thesis (Ph. D.)–Stanford University, 2000.
Pavlovicz, R. E., & LI, C. (2014). Investigation of protein/ligand interactions relating structural dynamics to function: combined computational and experimental approaches. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397220613.
Storch, J. and Thumser, A.E., 2010. Tissue-specific functions in the fatty acid-binding protein family. Journal of Biological Chemistry, 285(43), pp.32679-32683.
Fersht, A. (1998). Structure and mechanism in protein science: a guide to enzyme catalysis and protein folding. New York, W.H. Freeman.