Question: Hello, I need help on this Biomedical course homework. I would appreciate if you would me on this. Thank you. BME 201 - Spring 2024

Hello, I need help on this Biomedical course homework. I would appreciate if you would me on this. Thank you.

Hello, I need help on this Biomedical courseHello, I need help on this Biomedical course
BME 201 - Spring 2024 - Homework #11: Name: Due: 4/19/2024 at 11:59 p.m. Remdesivir is an antiviral medication that's been proposed as a treatment for patients with COVID-19. Recall from class that remdesivir is a nucleotide analog that's designed to interrupt the polymerization of viral RNA. It does this by terminating a growing strand of RNA being synthesized by viral RNA polymerase when that RNA polymerase mistakenly incorporates it into the growing RNA strand, instead of the proper nucleotide ATP. In order for remdesivir to be an effective drug, it should have a relatively high probability of being polymerized by viral RNA polymerase. For it to be a safe drug, it shouldn't have much interaction with human RNA polymerase, since sometimes it's nice to be able to express our own genes. Review our discussion in class on a drug's therapeutic window for more details. a) (40 Points) Let's consider this important property of drugs using what we know about Michaelis- Menten enzyme kinetics. We'll model the system according to the following: RNApol: RNA +remdesivir = RNApol: RNA : remdesivir - RNApol+ terminated RNA How does the above chemical equation relate to the standard E, S, and P in the typical Michaelis- Menten expression? i.e. What is E, what is S and what is P? b) (30 Points) Let's consider the reaction velocity dt to reflect the probability that an RNA strand is prematurely terminated. Do we want this probability to be higher for the viral RNA dependent RNA polymerase or human RNA polymerase? Why? c) (30 Points) The enzyme kinetic parameters for remdesivir/RNA polymerase have been studied in the context of ebolavirus and respiratory syncytial virus and published by Tchesnokov et al. (Table 1). The headers of Table 1 are EBOV (ebolavirus), RSV (respiratory syncytial virus), and human (h-mtRNAP). For the sake of this problem, let's assume that the kinetics of RNA polymerase for the novel coronavirus are identical to that of Ebola. Be sure to use the Remdesivir-TP values.Table 1 RNA polymerase selectivity values for remdesivir-TP nucleotide analogue. RNA Polymerase EBOV RSV h-mtRNAP Substrate ATP Remdesivir-TP ATP Remdesivir-TP ATP Remdesivir-TP Vmax" (product fraction) 0.84 + 0.027 (3%) 0.75 = 0.039 (5%) 0.76 # 0.022 (3%) 0.82 # 0.027 (3%) 0.98 # 0.018 (2%) 0.81 # 0.013 (2%) Km' (HM) 1.5 # 0.23 (15%) 5.7 # 1.1 (19%) 0.17 # 0.023 (14%) 0.50 # 0.089 (18%) 0.050 # 0.0037 (7%) 21 # 0.096 (5%) Vmax Km 0.56 0.15 19.6 0.035 Selectivity *(fold) Ref. 8 3.8 Ref. 2.7 Ref. 508 "Vmax is a Michaelis-Menten parameter reflecting the maximal velocity of nucleotide incorporation. . Am is a Michaelis-Menten parameter reflecting the concentration of the nucleotide substrate at which the velocity of nucleotide incorporation is half of Imax. " Selectivity of a viral RNA polymerase for a nucleotide substrate analogue is calculated as the ratio of the Vmax/Km values for ATP and remdesivir-TP. All reported values have been calculated on the basis of a 9-data point experiment repeated three times (n = 3) for natural ATP substrate and the substrate analogue remdesivir-TP for each of the enzymes. " Standard error associated with the fit. / Percent error. 8 Reference. Using MATLAB, plot the Michaelis-Menten curve (V observed (y-axis) versus the concentration of Remdesivir-TP (x-axis) for the velocity of the incorporation of remdesivir by viral and human RNA polymerase. Note that there is no code template this time, but you can use code from previous homework assignments if you want. Make sure EVERY line of code is commented and in your OWN words. Use the mean parameter values in Table 1. Graph the curves for viral and human RNA polymerase on the same semilogx plot. Use remdesivir concentrations from 10" to 10" uM for the X axis. (Review old homeworks and the 'logspace', 'semilogx', and "hold on' MATLAB commands for help). Include axis labels, a legend indicating which curve is which, and your name in the title. Paste the curve and your code into a word file (or this one). Your result should roughly look like the drawing below. Title w/ Name Virus y- label Human x-label

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