SOLUTION AT Australian Expert Writers
1. Student code_ UK R555
2. University/College Name_university of Bedfordshire
3. Topic if any……..practical portfolio.
4. Subject name_computational biology
5. Level-like Bachelor, Diploma or Master’s = Master
6. Word’s limits if any……2500 maximum 2650
7. Submission date_09 04 2021
8. Reviewer name & date before submission = aarti two practicals both add in one I need before 30 march
* Reviewer by Teacher’s NO
* Reviewer by Smart friend’s of the class. NO
9. Can we use outside sources? Use all relevant materials
10. Please attach only relevant course material or lecture notes, this is must
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Unit title & code
BHS008-6 Computational Biology
Assignment number and title
Assessment 1 (referral) Practical Portfolio
Weighting of assignment
Size or length of assessment
Unit learning outcomes
1..Demonstrate a depth of knowledge in the application of computational techniques to the modelling of structural and functional aspects of biological systems. Such an understanding will cover both Molecular and Systems levels of modelling.2. Show a critical awareness of the limitations of the techniques such as sequence alignment, homology modelling and systems modelling and apply these methods to model systems.
What am I required to do in this assignment?
You will present the results from the two practical classes In the first you will carry out a model sequence alignment, which demonstrates the application of the dynamic programming technique. You will then use the NCBI server to align two related sequences. Finally, you will map the sequence alignment data onto the three-dimensional structure of one of the proteins. In the second session you will use the molecular graphics package Swisspdbviewer to address a number of questions relating to the structure and function of a family of enzymes. This will introduce you to a number of graphical modelling techniques and will illustrate how proteins can be represented computationally (see protocol document) You will be expected to produce a laboratory report detailing your findings across both sessions. The report should be no more than 2500 words. Excessive word counts will negatively affect grading. The lab report should be structured like a research article in a scientific journal (see details below).
What do I need to do to pass? (Threshold Expectations from UIF)
Demonstrate the ability to carry out modelling tasks including sequence alignment and the use of molecular graphicsProduce a written report in the form of a scientific paper that discusses the content of the practical sessions
How do I produce high quality work that merits a good grade?
Outline Of Report Structure Your lab report should contain five sections; Introduction, Method, Results, Discussion and References. Each section should be clearly labelled. Clarity of English language and presentation is essential throughout. Introduction: This section should typically represent 20-30% of your report. It should summarise the published background literature relevant to this study. It must explain what your experimental study is about, and place it in context of the previously published literature. It should state the scientific aim of the study. Method: This section should typically represent 10% of your report. It should briefly summarise how the practical work was carried out. It should be written in the past tense and in paragraphs. It should contain sufficient detail to allow someone else to reproduce your experiment, but avoid unnecessary detail. Results and discussion: This section should typically represent the remaining 60-70% of your report. Data may be presented in tables, graphs, diagrams, or photographs as appropriate for your particular experimental study. Figures and tables should be separately numbered, and be clearly labelled. You should include written text to explain what your findings are and what is shown in the figures and tables. Results should describe your findings/observations, but not interpret their meaning. In the discussion you should interpret your results, explaining what they indicate. You should evaluate the quality of your data. You should identify any problems with the technique or data (if any exist) and suggest possible solutions. You should compare your findings to previously published findings or your expected findings, and should place your results in the context of published scientific literature. Your discussion should also include a reflection on your performance within the practical. What insights did you gain from the practical sessions; what problems did you have to overcome etc. References: You should include at least three peer-reviewed scientific journal articles or textbooks as sources. These should be listed in correct UoB/Harvard format in a single reference list. (see https://lrweb.beds.ac.uk/__data/assets/pdf_file/0009/557568/UoBHarvard17_18.pdf) The reference list should only contain sources that have been cited appropriately – e.g. (Smith, 2010) – in the main text of your report.
How does this assignment relate to what we are doing in scheduled sessions?
The assignment tasks are based upon the direct application of techniques that have been discussed in lectures. In addition, you will be expected to gain insight into the biological problem
How will my assignment be marked?
Your assignment will be marked according to the threshold expectations and the criteria on the following page.You can use them to evaluate your own work and consider your grade before you submit.
Pass – 40-49%
Pass – 50-59%
Commendation – 60-69%
Quality of understanding and analysis of scientific principles and knowledge base. (30%)
Understanding of scientific principles at a basic threshold level. Some evidence of a literature review.
Acceptable level of understanding of relevant scientific principles and knowledge base. Adequate review of relevant literature, though some omissions or tangents. A reasonable attempt to relate study to broader context and explain aim and approach.
A good understanding of the scientific principles and knowledge base. Literature review should be more critical. Context requires a more detailed approach.
A comprehensive understanding of the scientific principles and knowledge base. Detailed and focused review of previously published literature. Broader context of study clearly described. Experimental aim and approach well defined.
Data handling and presentation. (15%)
Data analysis is present but incomplete. Presentation is could be improved. Explanations of data superficial.
Data analysis is mostly correct with few errors or omissions. Presentation is generally clear and appropriate. Some attempt is given to explain what is being presented.
Data analysis is accurate, but not complete. Presentation is clear and appropriate. Clear explanation of what is presented is given. Good understanding of data analysis shown
Data analysis is accurate, thorough and complete. Presentation is clear and appropriate. Clear explanation of what is presented is given. Excellent understanding of data analysis shown.
Critical evaluation and discussion. (25%)
Evidence of reflection and evaluation of scientific problem and approach. More critical evaluation of cited literature is required. Demonstrates some ability to make evaluative links between the current scientific thought and the work in hand, but the evaluation is often rather superficial.
Satisfactory evidence of reflection and evaluation of scientific problem and approach. Some critical evaluation of cited literature, though at times a little shallow. Demonstrates some ability to make evaluative links between the current scientific thought and the work in hand, but the evaluation is sometimes rather superficial.
Demonstrates some ability to evaluate scientific problems and to make clear evaluative links between the current scientific thought and the work in hand. Shows good critical evaluation of cited literature.
Demonstrates a well-developed ability to evaluate scientific problems and to make clear evaluative links between the current scientific thought and the work in hand, which are capable of contributing to the advance of scientific knowledge. Shows excellent, deep critical evaluation of cited literature.
Written expression and structure. (20%)
Written expression is not always clear and arguments can sometimes be confused The structure of the work is satisfactory but planning could have been more thorough in parts.
Written expression is clear and arguments can be followed without undue difficulty. The structure of the work is satisfactory but planning could have been more thorough in parts.
Written expression is clear and concise. Arguments are put forward succinctly but the structure of the piece needs further planning to enhance its readability
Written expression is clear and concise. Arguments are put forward succinctly and the structure of the piece is well planned, well-thought out and logical, enhancing its readability.
Use of literature and referencing.(10%)
A limited range of literature cited, with considerable reliance on secondary sources. Incorrect use of UoB Harvard referencing format or lack of appropriate citations within text of report.
A range of primary sources is accessed. Possible errors in the use of the UoB Harvard formatting of citations and reference list.
A broad range of primary sources is accessed. Possible errors in the UoB Harvard referencing format.
A broad range of primary sources is accessed. Correct Journal of Cell Science formatting of citations and reference list used throughout.
BHS008-6 Computational Biology
In lectures we have considered what sequence analysis is and have shown how it can be used to probe evolutionary problems and its importance in protein structure prediction and modelling.
In this practical class we shall consider three things:
how the dynamic programming method works;
alignment of two serine protease sequences;
relating a sequence alignment to three-dimensional structure.
The dynamic programming method proceeds through three stages. First the two sequences are placed on the two axes of a grid and this matrix is filled to indicate the relationship between each residue in sequence 1 with all residues in sequence 2. When completed this is known as the comparison matrix.
Next, the comparison matrix is converted in to the ‘maximum match matrix’, which shows the highest scoring path starting from a given residue. Here we start from the bottom right hand corner of the comparison matrix; the score in a particular grid point is added to the highest scoring box in the following row and column. Once this has been done, the highest scoring path can be extracted from the matrix, defining the alignment.
You are given the two sequences ADGDQASY and ADCDQWSY as examples. We will use the identity relation to construct the comparison matrix (1 if i=j, 0 otherwise).
Using the two grids below create the comparison and maximum match matrices. Finally, give the optimum alignment for the pair of sequences.
Maximum match matrix
2. Sequence Alignment
In this exercise we shall take the two sequences below and align them using the BLAST software. We will access this using a server at NCBI (the National Centre for Biotechnology Information) in Maryland, USA.
To start, direct your web browser to
This page provides the interface to the alignment procedures. Here you can do two things: you can search your query sequence against entire data bases of other protein sequence to find matches, or you can seek an optimal alignment between just two sequences. We will do the latter. Below are the sequences for Bovine cationic trypsin and Rat tonin
Bovine cationic trypsin
Paste these two sequences into the sequence boxes and initiate the alignment using the ‘BLAST’ button.
Within a few minutes an alignment should be shown.
3. Structure/Sequence Analysis
In the final exercise we shall use the information from this alignment to verify the hypothesis that higher degrees of conservation are seen in the protein core and that insertions and deletions only occur in the loop regions. To do this we will use the SwissPDBViewer (spdv) software.
To start, you will need to download the coordinates of trypsin (5ptp) from the protein databank (www.rcsb.org). Once the programme has loaded you should read in these coordinates. Using the control panel, set the display to ‘carbon alpha ‘ trace. Find the regions of regular secondary structure and mark these on your alignment. Next, colour the conserved residue positions on the trypsin structure. Comment on your observations. Do they conform to our hypothesis?
Your write-up should contain the following sections: an introduction of no more than 500 words on sequence analysis/alignment; results which comprise your comparison and maximum match matrices together with the alignment, and your trypsin/tonin alignment; a discussion commenting on the details of the sequence alignment in relation to the three-dimensional structure.
Practical 2 – The Serine Protease Active Site
A prerequisite to understanding mechanistic aspects of enzyme action is a proper appreciation of their structure. The three-dimensional arrangement of the catalytic groups or the arrangement of residues that confer specificity cannot be inferred from sequence information; often these features are composed of amino acids that might appear at first sight to be randomly distributed through the primary structure.
In this practical we shall be using molecular graphics methods to investigate various aspects of the structure and activity of the serine protease class of enzymes. While we shall be focussing our attention on the best-characterised group, the digestive enzymes, it is instructive to make comparisons to other independently evolved enzymes, the bacterial enzyme subtilisin and the catalytic antibody 17E8, which share the same functional motifs and catalytic mechanism.
Chymotrypsin is a digestive serine protease that is synthesized as a 245 residue zymogen, chymotrysinogen, before being activated through proteolitic removal of the N-terminal 15 residues. Conventionally then, the protein chain is numbered from position 16 although this is the N-terminal residue of the active form.
Prior to looking at functional aspects of this protein it is worthwhile to spend some time simply looking at the overall structure; at first glance the protein may seem globular but if the amount of information that is displayed is reduced to just the Ca atoms of each residue it becomes clear that the protein actually comprises two distinct structural domains separated by a cleft which contains the active site. In this display mode the location of the individual regular secondary structure elements is also much more apparent; note that the protein contains very little helical structure while the two domains appear to have a high degree of b-structure.
1. The Active Site
From this point we shall attempt to build up a picture of the important functional aspects of chymotrypsin in the context of the complete protein structure. First, we shall introduce the active site groups. These can be redisplayed using the Control Panel, setting the specification to sidechain and indicating the residue numbers (57, 102 and 195). Zooming in on these features should allow measurement of the critical distances between the His and Ser and the Asp and His. Next redisplay the bound peptide (residues A250-A252). This peptide represents the product peptide following regeneration of the active site. Calculate the distance from the active Ser oxygen to the C-terminal carbonyl carbon of the peptide (The Distance option).
The next important feature of the active site is the position of the ‘oxyanion hole’, which is crucial in driving the catalytic reaction through stabilisation of the developing transition state. The residues responsible for this effect are Ser195 and Gly 193. Display these residues and colour them by atom colour to locate the positions of the backbone nitrogens. Note the distances from these nitrogens to the peptide carbonyl oxygen. What do these distances imply?
2. Peptide Specificity
The three main digestive serine proteases each show specificity for different residues immediately preceding the scissile bond. In the case of chymotrypsin this specificity confers a preference for bulky hydrophobic sidechains such as tryptophan and phenyalanine. The bottom of the specificity pocket also contains a Ser at position 189 which can hydrogen bond to the sidechain hydroxyl of tyrosine.
Display and colour this residue together with the amino acids that line the mouth of the specificity pocket (residues 214–216). It should be clear that the mouth of the binding pocket is wide enough to allow large amino acid sidechains to bind.
Finally, a number of attempts have been made to convert trypsin into an enzyme with chymotrypisn like specificity, that is to say one that binds hydrophobic residues rather than basic residues such as Arg or Lys in the specificity pocket. Making this simple mutation has failed to produce the required result. However, it was shown that if the residues in the two loops including positions 185–188 and 221–225 were also mutated then the specificity could also be altered. Identify the location of these loops and the amino acid types. Compare these to the equivalent residues in trypsin (trypsin.pdb)
Subtilisin and 17E8
Repeat the above procedures for the active site of subtilisin and the catalytic antibody 17E8. The catalytic triad in subtilisin contains residues 32, 64 and 221; the oxyanion hole comprises the sidechain of Asn 155 and the backbone NH of Ser 221; the mouth of the specificity pocket is bounded by residues 125–127.
The antibody’s active site contains only an active diad (Ser H99 and His H35).
Superposition and Comparison of Structures
Although all three proteins carry out the same catalytic reaction, their three dimensional structures look very different. Using the atoms of the imidazole ring of the catalytic histidine, superimpose the three structures. Note any further similarities in their binding sites. Focus on those residues that might be responsible for conferring specificity. Base your assumptions on residues that might superimpose near to residue 189 of chymotrypsin.
Harvard Referencing Guidelines for Students
Feedback This report has nothing to do with the practical. there is nothing I can mark. This a wrong submitted content, therefore the report can’t be marked.
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