Potential Inhibitory Activity of Naringenin Against Zika Virus Molecular Docking - Nursing Assignment Help

Assignment Task

4MOLECULAR DOCKING PROJECTx
4.1 Introductionx
4.1.1 Problem statementx
4.1.2 Objectivesx
4.1.3 Scopex
4.2 Literature reviewx
4.3 Material & Methodsx
4.4 Results & discussionx
4.5 Conclusionx


4.1.1 Problem statement
This subsection should consist of thesis statement (statement of issues), identified solutions, 5Ws (what, who when, where and why) the problems occurs, vision of your study and concluding remarks of the problems.
The statement should begin with clear description of the issues including vision, issue statement and method used to solve the problem. The description then followed by the 5Ws of the problems that comprises words to keep the effort focused, represent solvable problems.
For problem statement, one should use words such as identify, define, relate, describe, review, justify, indicate, formulate, explain, compare, contrast, suggest, interpret, analyze, assess, construct, apply, demonstrate, illustrate, categorize, deduce, create, resolve, debate, propose, differentiate, argue, derive, design, evaluate, establish, conceptualize, suggest, integrate, compile, develop, challenge, consolidate, clarify, criticize, ascertain, appraise, calculate, recommend. These words show some examples of good outcomes based verb. Verbs such as understand, explore, investigate, examine and discuss are poor verbs as they describe processes, not outcomes. It is not convincing when discuss something endlessly without ever having to make recommendations, draw conclusions or offer a result. Students might be exploring, examining or discussing as part of the process, but they cannot be the end result of the research, which should be more tangible.
In some cases, the postgraduate students are required to formulate their hypothesis in the problem statement section. For that case, the following discussion will emphasize the fundamental of hypothesis.
4.1.2 Objectives
i) To examine the interaction between Naringenin ligand and few protein receptors of ZIKV (NS3 helicase, NS5 polymerase and Envelope protein).
ii) To compare the best binding affinity of Naringenin towards the targeted ZIKV protein via the molecular docking.
4.1.3 Scope of study
This study is focus on the protein-ligand molecular docking by using AutoDock Vina and its analysis of interaction between a natural product known as Naringenin and few protein receptors of ZIKV that are NS3 helicase, NS5 polymerase and Envelope protein (PDB ID: 5GJC, 5U04 & 5JHM). Besides, the results of the binding affinity of Naringenin towards the protein receptors in each poses will be compared to select the best binding conformation that is suitable for ZIKV drug design.
4.2 Literature review
The purpose of this section is to provide the literature review of the study. This section begins with the general info of molecular docking studies followed by the ZIKV infection mechanism and how the Naringenin flavonoid compound can be the best candidate for the drug design.


4.3 Material & methods
This section states the software requirement in order to carry out the experiment and describes the activities that were executed in this study including structural retrieval & preparation of both ligand and protein as well as defining the active site and last but not least, performing molecular docking.
4.3.1 Structural retrieval and preparation
The NS3 helicase, NS5 RNA dependent RNA polymerase (RdRp) and envelope structure of ZIKV protein were retrieved from the Research Collaboratory for Structural Bioinformatics, Protein Data Bank (RCSB, PDB). The 3D-structures of these protein receptors were downloaded in PDB file format (PDB ID: 5GJC, 5U04 and 5JHM). Besides, 3D structure of the ligand which is Naringenin natural compound was obtained from National Center for Biotechnology Information (NCBI), PubChem Database in Spatial Data File (SDF) format.
After all the protein receptors and ligand structure were acquired, then the protein and ligand preparation can be performed. So as to not be confused, the separate folder of each protein receptor were created to locate the files individually. All the protein receptor was modified by removing the HETATOMS from the structures to get accurate results. Also, chain B in the envelope protein structure were removed because only chain A were used to perform docking in this study. In this step, the PDB files of the target protein were opened by using WordPad and the file has been saved after removing those HETATOMS and other chain. For ligand preparation, the files that already been obtained from PubChem Database was converted to PDB file format by using Open Babel software.

The following part were the input of configuration file created in the Notepad (respective receptor protein):
ZIKV NS3 helicase in complex with ATP (5GJC)
receptor = 5gjc_receptor.pdbqtligand = naringenin_ligand.pdbqtcenter_x = 5.828
center_y = 16.665
center_z = 4.783
size_x = 40
size_y = 40
size_z = 40
out = vina_outnaringenin.pdbqtlog = lognaringenin.txt
exhaustiveness = 8
Crystal structure of ZIKV NS5 RdRp (5U04)
receptor = 5u04_receptor.pdbqtligand = naringenin_ligand.pdbqtcenter_x = 26.149
center_y = 65.156
center_z = 109.091
size_x = 40
size_y = 40
size_z = 40
out = vina_outnaringenin.pdbqtlog = lognaringenin.txt
exhaustiveness = 8
Crystal structure of ZIKV Envelope protein (5JHM)
receptor = 5jhm_receptor.pdbqtligand = naringenin_ligand.pdbqtcenter_x = - 22.726
center_y = - 69.060
center_z = 3.249
size_x = 40
size_y = 40
size_z = 40
out = vina_outnaringenin.pdbqtlog = lognaringenin.txt
exhaustiveness = 8

4.4 Results & discussion
As was described in the previous subtopic 4.3 Material & Methods, the completion of the proposed method was evaluated by using several software like Microsoft Excel to plot the average of binding affinity, Discovery Studio Visualizer as well as LigPlot+ to visualize and examine the interaction. The analysis of these experiment was assessed in term of the binding affinity and the interaction that present between the ligand and protein according to its poses.
4.4.1 Molecular docking analysis
The binding potency of Naringenin to the ZIKV target proteins were tested by using AutoDock Vina as mentioned previously. Figure X illustrates the average docking scores (kcal/mol) calculated by using AutoDock Vina for the three protein receptors; ZIKV NS3 helicase, ZIKV NS5 RdRp and ZIKV E protein. The horizontal error bars represent the calculated standard deviation from the mean.

Figure X.The average binding potency values that were calculated by using AutoDock Vina as a results of docking from Naringenin inhibitor against the targeted proteins.
Based on the results, envelope protein of ZIKV shows the lowest average in docking energy followed by NS3 helicase and NS5 RdRp of ZIKV. The best conformation for these three protein still considered in the good range in which the predicted binding affinity of NS3 Helicase ZIKV protein was -7.9 kcal/mol. Pro 320, Asp 410, Glu 413, Lys 431, Asp 481, His 484, and Lys 514 were found actively interacting with Naringenin ligand. The predicted binding affinity of NS5 RdRp of ZIKV was -7.0 kcal/mol and Tyr 609, Asp 666, Cys 711, Ser 798, Ile 799 and His 800 were found at the active site. The predicted binding affinity for the envelope protein of ZIKV was -8.5 kcal/mol. Gly 145, Leu 300, Lys 301 and Val 364, were found to interact with the ligand. The docked compound in the pocket region of Naringenin interacting with the active sites of NS3 helicase, NS5 RdRp and E protein of ZIKV were illustrated in Figure Y.

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