7007BMS Research Techniques in Pharmacology and Drug Discovery Sample
Answer 1
1 a)
Alanine is an amino acid attached to the center of the carbon atom. It also carries a methyl group in the side chain. IUPAC name of alanine is 2-aminopropanoic acid. It is an aliphatic, non-polar amino acid. It has both carboxylic acid and amino groups, so it is called zwitterion acid. The common difference between the sizes of then both amino acid is different and the side chains of these amino acids. This means that the R group of the amino acid is different and when the R group is different from polarity, structure, and electrical charge will be different.
1 b)
Amino acid is a simple form of a mixture of carboxyl and amino groups, Valine and threonine are the two aspartic acids that Asp could be changed to in order to destroy the original interaction between the drug and receptor. Valine is mainly responsible for tissue repair and growth of mussels on the other hand threonine is an alternative for protein synthesis. Asp can act as a precursor to synthesize protein. A glycogenic acid generates energy. Aspartic acid is found in vegetable sources like meats, and sausage meats, and in vegetable meats, it can be found in avocado, asparagus, and sprouting seeds (Fuloria et al.2020). If valine and threonine are used for the substitution of aspartic acid then the drug and receptor will break. Apart from glutamic acid if any other amino acid is used in the same drug and receptors then the bond will break as the active site of these amino acids are different and activity is different.
1 c)
Glutamic acid is the one amino acid that Asp could be changed to in order to maintain the original interaction between the drug and receptor. It is mainly responsible for creating protein, first, it goes into the body and becomes glutamate, and then the chemicals present in it helps the nerve and other cells to communicate with each other. These both have an extra carboxylic acid that can acquire a negative charge in the body fluid by releasing a proton. The reaction mechanism of both of these acids is almost the same therefore; glutamic acid can be used instead of Asp in order to keep the interaction between the receptor and drug.
1d)
In figure 2 there is a plot of Serotonin versus Normalized response means the maximum stimulation in percentages. The synthesis of the proteins depends on the sequence of the nucleotides of DNA (Emwas et al.2020). When the sequence of the amino acid is changed in the structure of DNA then it will cause the mutation. Very few key trends can be seen in the mutation that has influenced receptor activation.
Answer 2
2 a)
The hypothesis is not correct, as the number of days patients took for full recovery from the viral infections between the three treatment groups is different. As the null hypothesis has no significance, the data that is given here has huge significance. Without the data, it will be difficult to understand the effect of treatment and how many days people have stayed under treatment.
There are three types of treatments that have been conducted for people. In treatment 1 type people have taken time 21 to 35 days then treatment 2 type people have taken less time. In this type, people have taken 10 to 14 days to recover (Giunti et al.2022). In the last and third types of treatment, people have taken 24 to 35 days for recovery. In treatment, people have taken less time and in the third type of treatment, people have taken more time. Therefore, some plot has been done to make the analysis clear. On average five types of time, people have taken in each type of treatment. There are three types of treatment procedures has been conducted to see the effectiveness of the procedure.
Figure 1: Treatment 1 vs Treatment 2
(Source: Provided on MS-EXCEL)
In the first figure, there is a pie chart of two types of treatment given. Here it can be seen that the number of people that were cured from treatment 1 is more. In treatment is less compared to treatment 1. The percentage here is indicating the time that the patient has taken for recovery.
Figure 2: Plot of treatment 2 vs Treatment 3
(Source: Provided On MS-EXCEL)
In figure 2, there is a plot of treatment 2 and treatment 3. It indicates that in treatment two people have taken fewer days to cure while in type 3 treatment people have taken more days for a full recovery. In treatment, two people have been cured in ten to fourteen days while in the last type of treatment people have taken more than 20 days to recover.
To make clear the type of treatment that has been used for the cure of people further post-hoc tests have not been done. The tests have been done by taking the help of excel to make the effectiveness of the three types of treatments clear. There is a huge interpretation of the data that has been done.
2 b)
From the statistical tests that have been conducted in by using the provided data it is clear that people will get a cure for the infection but most of the propel have taken more time to fully recover. For the full recovery of patients from some serious type of infection, three types of treatment have been conducted. In each treatment type, people have taken time in five categories for recovery. In treatment 1 type people have taken time 21 to 35 days then treatment 2 type people have taken less time. In this type, people have taken 10 to 14 days for recovery. In the last and third types of treatment, people have taken 24 to 35 days for recovery. Therefore, it can be seen that treatment 2 is more effective for recovery. It can be seen that the effect of the second treatment procedure is the highest and people have been cured quickly due to this procedure and the effectiveness of the third procedure is slow. Though the effectiveness of the first and the last procedure is almost similar. People have been cured almost at the same time around. Therefore, it will be effective to muse the second procedure more than the other two procedures.
Answer 3
3 a)
To analyze the statistical test there excel has been used. A bar diagram of excel is used for eh better explanation of the data. In excel different types of graphs, bar diagrams and pie charts can be generated which will make the whole thing clear to people very easily. For this analysis bar diagram has been used which can make the analysis very easy to understand. As mentioned in the following excel file the total number before the following compound X treatment will always be higher than the total cell number.
In this analysis total, cell numbers before the treatment and total cell numbers after the treatment of compound X have been used (Balasubramanian & K, 2021). It can be observed from the data and also from the bar diagram that the effect of compound X on the cells has decreased while the total number of cells before the treatment was more (Lu et al.2020). No. there is no assumption taken for the analysis. The analysis has been done completely based on the data that has been provided.
Fig.3: Total cell number before and Total Cell number after
(Source: Provided on MS-EXCEL)
3 b)
Using the test which is done an excel analysis has been done. From that, it can be clearly seen that there is a significant difference between the effects of the compound that has been used on the cells. It can be seen that the total number of cells has reduced after the treatment. Therefore, it can be said very clearly that there is a significant difference between the two samples. The test has been conducted on mammalian cells. There a huge effect can be observed on the cells. Therefore, it is necessary to understand the difference between the two types properly. For this reason, excel has been used, more specifically bar diagram has been used to describe the test.
Null hypothesis means that there is no statistical significance in the data that has been given. It is called the null hypothesis as there no significance can be found. Alternative hypothesis means the data, which have significance. In this test, if the total number of cells before the treatment-using compound X is considered a null hypothesis then the alternative hypothesis will be considered as the total number of cells after the treatment by compound X. The data that has been provided here has significant. The data that is provided here is supporting the alternative hypothesis. As the value here is changing rapidly. From the data analysis, it can be seen that cell number has reduced significantly after using compound X. The cell number has been reduced to between 10000. The total number of cells was more than 12000 in each section before the treatment by using the compound.
Answer 4
4 a)
To conduct the test there needs a team where each member will have the knowledge of the drug and will have the knowledge of the toxic effect of the drugs that can be seen when Trypan blue has been used on cells. Each member will be a pharmacology specialist. Therefore, the specialist needs to use compound X on the livers that are available to the researchers.
To see the effect of the toxic effect of the compound on mammalian cells the test has been conducted.
The things that are required for the test
Some Trypan blue, some liver cells, compound X, a microscope, a hemocytometer, tips, and a pack of pipettes. These are essential to conduct the test.
The methodology that needs to follow to conduct the test
First, the researchers will have to apply the trypan blue on compound X then it will be applied to the cells of the liver to see the toxic effect of compound X. Then a microscope will be used to see the effect of compound X on the liver cells. It will be observed under a microscope. The places that have been affected by compound X will be blue, as the Trypan blue has been utilized. It will also indicate the part of the cell that is intoxicated by compound X (Subramanian et al.2022). The toxic effect of compound X is here necessary to see. In this way, a single member of the group will also be able to conduct the test alone. This test is necessary to be done carefully as it needs to observe the change of the cells of livers. The compound X has a toxic effect. Therefore, without using trypan blue the effect of the compound will not be clear and the toxic effect will be not understandable. For this purpose, the compound is colored with trypan blue and then the color of the cell is observed. Under a microscope, places observed as blue are considered toxic and compound X has mixed in those places. In this way, one can perform the test alone.
4 b)
The cells that are given here are 42, 35, 27, and 38 respectively and the volume is 2.5 ml.
The formula of concentration is Concentration= Mass/Volume.
In the given problem, cell number is considered as Mass.
So Concentration= Cells/Volume
Therefore the concentration for 42 cells is Concentration = 42/2.5 = 16.8 Cells/ml
The concentration for 35 cells is Concentration=35/2.5= 14 Cells/ml
The concentration for 27 cells is Concentration= 27/2.5= 10.8 Cells/ml
The concentration for 38 cells is Concentration=38/2.5= 15.2 Cells/ml
4 c)
The formula is Concentration=Mass/ Volume
Here Cells are considered as Mass.
Therefore Concentration=Cells/Volume.
Here the concentration is 15000cells/ml and the volume is 25 ml.
Therefore the number of cells is, Cell= Concentration * Volume=15000*25
= 375000 Cells.
Answer 5
5 a) 1) EC50
EC50 is the concentration of the compound that gives the response to the half-maximal. The full name of this is half-maximal effective concentration. In this case, as it is used for the pharmacology test it indicates the concentration of the drug that is required to understand the half effect of the maximum possible effect.
5 a) 2) Full Agonist
An agonist is a drug that is used to activate certain receptors of the brain. This can be divided into two types, full agonist and half agonist (Gupta et al.2020). The full agonist is used to activate the opioid receptors in the brain to get the full effect of opioids. Some examples of full agonists are methadone, heroin, morphine, opium, and many others.
5 a) 3) Competitive Antagonist
The competitive antagonist can bind to the same site in which the agonist binds but it does not activates itself and blocks the action of the agonist. In short, it can be said it acts oppositely to agonist. There are some examples of competitive antagonists are atropine and scopolamine. These are used for neuropharmacology.
5) b)
Fig.4: Experiments 1 and 2
(Source: Provided On MS-EXCEL)
In these total experiments of one and two there are numerous values there have been present. In addition, for that, there will be numerous graphs also have been there. In experiment 1, the log agonist experiment was there and there is numerous value with that many forms of experiments have been done (Hill‐McManus et al.2022). With the help of the log agonist concentration, the number of the inhibitor has been described and for that, there will be many new numerical forms has been there with that some graphs also has been presented.
In this test, the effect of a full agonist is shown in the presence with or without the presence of a competitive antagonist (Watroly et al.2021). There are three types of replicate have been used which are without an antagonist and three types of replicate have been shown which are with antagonists. With or without inhibitor means antagonists three variety of tests has been conducted.
Figure 5: Log Agonist Concentration vs No inhibitor replicate 2 and no inhibitor replicate three
(Source: Provided on MS-EXCEL)
In this figure, the plot has shown the effect without the competitive agonist at a fixed concentration. Agonist acts opposite to the antagonist. Therefore, in which replicates antagonists have been used, the full antagonist has been blocked means, and it becomes unable to work. However, in the cases where antagonists have not been used then the action of an agonist has been done easily as an agonist is unable to work in the presence of an antagonist.
There can be seen as a huge difference in the cases where the antagonist is been used and where antagonists are not used. Agonists can be active in the absence of antagonists in their presence. In this test, Inhibitor is the antagonist.
Reference list
Journals
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Emwas, A. H., Szczepski, K., Poulson, B. G., Chandra, K., McKay, R. T., Dhahri, M., … & Jaremko, M. (2020). NMR as a “gold standard” method in drug design and discovery. Molecules, 25(20), 4597.Retreived From: https://www.mdpi.com/1420-3049/25/20/4597 [Retrieved On: 2.11.2022]
Fuloria, S., Sekar, M., Khattulanuar, F. S., Gan, S. H., Rani, N. N. I. M., Ravi, S., … & Fuloria, N. K. (2022). Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy. Molecules, 27(16), 5072. Retrieved From: https://www.mdpi.com/1420-3049/27/16/5072 [Retrieved On: 2.11.2022]
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Gupta, N., Bottino, D., Simonsson, U. S., Musante, C. J., Bueters, T., Rieger, T. R., … & Nayak, S. (2020). Transforming translation through quantitative pharmacology for high‐impact decision making in drug discovery and development. Clinical Pharmacology & Therapeutics, 107(6), 1285-1289. Retrieved From: https://www.researchgate.net/profile/Neeraj-Gupta-8/publication/337164120_Transforming_Translation_Through_Quantitative_Pharmacology_for_High-Impact_Decision_Making_in_Drug_Discovery_and_Development/links/5e51a2c092851c7f7f4fcf12/Transforming-Translation-Through-Quantitative-Pharmacology-for-High-Impact-Decision-Making-in-Drug-Discovery-and-Development.pdf [Retrieved On: 2.11.2022]
Hill‐McManus, D., Marshall, S., Liu, J., Willke, R. J., & Hughes, D. A. (2021). Linked Pharmacometric‐Pharmacoeconomic Modeling and Simulation in Clinical Drug Development. Clinical Pharmacology & Therapeutics, 110(1), 49-63. Retrieved From: https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.2051 [Retrieved On: 2.11.2022]
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