Structural Bioinformatics Assignments - Assignment Example

Structural Bioinformatics assignment Name University November 2014 Table of Contents 1.Swiss-PDB viewer 3 2. X-ray crystallography and NMR spectroscopy 5 1. Swiss-PDB viewer The aspects of structure for the protein 3AJ8.pdb: A).The resolution of the protein is high resolution and it shows that the protein structure is a 3D structure which requires more energy to break. This is because it has Ligand Interactions and 3D Structure Inspector B). Explain if this structure would provide a good structural template or homology modelling. Support your answer with appropriate details. The protein structure to be able to under go homology modelling, it has to low- resolution. In this case it is a high resolution. C. The following is an excerpt from the 3AJ8 pdb file. HELIX 6 6 SER A 138 SER A 151 1 14 and HELIX 7 7 ASP A 165 ARG A 167 5 3 SHEET 1 A 2 ALA A 2 GLN A 3 0 SHEET 2 A 2 TYR A 23 TYR A 24 -1 O TYR A 23 N GLN A 3 Describe the full details of the structural information contained in the extract. You should particularly note the number, types, theoretical lengths (alpha carbon to alpha carbon), theoretical number of main chain hydrogen bond connections, and start and stop positions of the structures. Show any calculations you may make and clearly explain your reasoning. D. Helix 6 in 3AJ8 is described by Deep View as starting from Ser139 and finishing at Ser150. Explain how this slight difference may arise. The differences are as result of changes in parameters like temperature. E. Given the helix Ser139 to Ser150 in Deep View how many hydrogen bonds does Deep View show and how does this compare with the theoretical number of hydrogen bonds? Explain any differences and show an appropriate image of the hydrogen bonds in the helix. F. If the angle for the hydrogen bond detection threshold was increased to 110° in Deep View (when hydrogens are not present in the structure) how many hydrogen bonds are subsequently detected by Deep View in the Ser139-Ser150 helix? Explain any differences between this number and the previously shown number of hydrogen bonds in (E). Include in your answer a brief explanation of the basis of the algorithm, and parameters, used by Deep View to detect hydrogen bonds. Show an appropriate image of the hydrogen bonds in the helix. G. Investigate the general conformations for the peptide bonds linking residues 170,171,172, and 173. Explain the significance of these conformations and if they are what you would expect based on your knowledge of amino acid and protein structure. Provide an appropriate DeepView image to support your answer. H. Fully describe, with supporting evidence, the specific kind of secondary structure described by residues 170,171,172, and 173. I. Carefully investigate residue 63 in the pdb file and explain what you notice about the ATOM record of two of its constituent atoms (ignore the ANISOU records). What particular column in the ATOM record is designed to describe the situation for the affected atoms? List all othe residues (residue name and sequence position) in the protein that demonstrate a similar situation. J. In the Chou and Fasman2 secondary structure prediction method proline was described as a ‘strong helix breaker’. Does this necessarily mean that proline should not be found in any helix? Use information from the 3AJ8 structure to support your answer. Proline is amino acid which does have a strong bond with hydrogen meaning that can not donate the hydrogen bond thus it is not a strong helix breaker. It will cause helix to have a bend because it does not have hydrogen bond. 2. X-ray crystallography and NMR spectroscopy Another confirmation of the quantization of EM radiation is found in the production of x-rays. In the X-ray crystallography it causes the emission of electrons; in an x-ray tube, electrons incident on a target cause the emission of EM radiation. Electrons move through a large potential difference V to give them large kinetic energies=eV. In the target, they are deflected as they pass by atomic nuclei. Sometimes an x-ray photon is emitted; the energy of the photon comes from the electron’s kinetic energy, so the electron slows down. The x-rays produced in this way do not all have the same frequency; there is a continuous spectrum of frequencies up to a maximum, called the cut-off frequency. Typically an electron emits many photons as it slows down; each of the photons takes away part of the electron’s kinetic energy. The maximum frequency occurs when all of the electron’s kinetic energy is carried away by a single photon: In the spectroscopic analysis of the light emitted by a discharge tube, the light first passes through a thin slit. Then it passes through either a prism or a grating so that light of different wavelengths emerges at different angles. While the light emitted by a hot solid object forms a continuous spectrum. Angstrom discovered that the light from a gas discharge tube forms a discrete spectrum. A discrete spectrum is also called a line spectrum because each discrete wavelength forms an image of the slit; the spectrum appears as a set of narrow, parallel lines of different colors with dark space between the lines. In addition to examining the light emitted by the gas, scientist also studied the light absorbed by gas. A beam of white light is sent through the gas and transmitted light is analysed with a spectrometer. The resulting absorption spectrum is the continuous spectrum expected for while light except for some dark lines. Most wavelengths are transmitted through the gas, but the dark lines show that a few discrete wavelengths are absorbed. The wavelengths absorbed are subset of the wavelength emitted by the same gas when in a discharge tube. Each element has its own characteristic emission spectrum. For instance, the characteristic red colour of neon sign is caused by the emission spectrum of neon. Scientists soon began to use spectroscopy to identify the elements present in substances. Many previously unknown elements were discovered through spectroscopy. Cesium was named fro its bright blue spectral lines; rubidium was named for its prominent red lines. Turning their spectroscopes toward the sun and stars, scientists identified elements such as helium, which had not yet been discovered on earth. The spectra of most elements show no obvious pattern but hydrogen-the simplest atom-does show a striking pattern. 3. Figure below shows how the dipole within a water molecule may be Represented. A. Use Figure to show the parallel orientation of the dipoles of two water molecules B. Use Figure 1 to show the antiparallel orientation of the dipoles of two water molecules (0.5 marks) C. The formula for a dipole-dipole interaction energy is as follows: E = µ1µ2θ’/Dr3 – {3(µ1r θ’’)(µ2r θ’’)}/Dr3 Where E = potential energy of the dipole-dipole interaction µ1µ2 are dipole moments of dipole 1 and 2 respectively θ’ and θ’’ are functions of the orientation (angles) of the dipoles relative to each other D is the dielectric constant of the medium r is the distance between molecules This formula can be seen as a ‘left hand’ part and a ‘right hand’ part. The right hand part is a subtraction of {3(µ1rθ’’)(µ2rθ’’)}/Dr3. Describe the general relationship of potential energy to the parameters and variables shown by the ‘left hand’ part of the dipole-dipole interaction formula. The relationship of potential energy to the parameters and variables shown by the ‘left hand’ is of non-linear nature. D. Use the Excel spread sheet to calculate the relationship between interaction energy and distance in a dipole-dipole interaction between the two water molecules when: (i) their dipoles are oriented antiparallel to each other. (ii) their dipoles are oriented parallel to each other. (1 mark) (iii) Briefly explain how we can seemingly ‘ignore’ the ‘right hand’ part of the dipole-dipole interaction formula to describe the general relationship of a dipole-dipole interaction. E. Can a dipole-dipole interaction be considered a short, medium, or long range interaction? Explain. Dipole-dipole interactions can be short-range interactions because energies between the falls off as 1/r3 power. Meaning that they have a complicated angular-dependence, 4. Discuss the following statement: “The relationship between structure and function appears to be a many-many relationship”. What does this statement mean and what issues does this involve for discovering the function of a protein? You may use tables to describe this structure to function issue. Many-many relationships of protein molecules imply that the chemical structure is connected to many molecules therefore breaking the bond become difficult. Some of the structures are bonded. Many-many relationship means that discovering the functions of a protein will require more energy than when it is many-one or one-one. 5. The structure superposition of two or more protein structure and determination of evolutionally relatedness. Protein structure re-alignment is important in determining the relationship between two proteins from the way it is arranged. If the structural alignment similarity will indicate some evolutionary relationship between the two proteins. This is also important when determining the source of the protein. One needs to do sequence structure mapping in order to determine whether they are related. It’s no secret that this system of re-alignment is used to determine the evolutionary relationship. The following formula is used to determine structural re-alignment: 6) i). structural bioinformatics involves the use of protein RNA and DNA structures to understand the biological processes. The structural bioinformatics is used in drug discovery by looking at the structure of components. In order to have a new drug one is able to manipulate molecular structure with the intention of increasing or decreasing potency. This increases the speed of understanding and designing the drug the sciences looks at the human genome and not the molecules then he begins to develop relating druggable targets. This leads to discovery of a drug that is used to cure diseases. ii). In order for anything to be known as a drug it must have the following characteristics; -a certain size and molecular weight ranging between 100-1000, they have also small pores of a epithelial lining, it should also have ionization constant. Ionization constant (pKa) means that the drug cannot be ionized fully in any fluid, whether acids or fluids. This means the drug’s ionization can be easily be determined using the following formula. % ionized drug =100/1+10(pKa-pH) % ionized drug =100/1+10(pH-pKa) The ionization constant has an impact during absorption in the body, removal through excretion from the body and how it is distributed in the body. For example, aspirin is easily absorbed in the body due to its low ionization constant. -another characteristic of a drug is structure activity relationship-during absorption the structure of any component is altered, this means a drug must have a chemical structure which is easily altered for it to qualify as a drug. This structure must be able to be transformed by the enzymes of the body through metabolism. This should be done directly or indirectly. The drug should also have the ability to change the nervous system and thus if overused can be said to be abused. iii). the use of QSAR-is used to identify the chemical structure of a protein DNA. This is done by regression models whereby a model is created to help scientists have a formula which they will use in calculating a molecular structure. This statistical method was used long time ago in discovering the chemical structure of components. The values would be clustered close to the process average, but some of the values would vary somewhat from the mean. If we turn to the process and take samples and compute the mean in each molecule, one would discover that these values also vary, just as the individual values varied. They too would have a distribution of values. This has that there is variability in chemical structure when whole-genome association analysis was done. This indicated some inconsistency in genotype when considering common deletion polymorphisms. The purpose was to find genomic variation information that could be used to find economical genetic traits. 7. ‘Molecular Dynamics Engine’ simulator window Describe and explain what you see for the following (a) Number of molecules surrounding the selected molecule The number of molecules surrounding the selected molecule is 3. (b) What physical molecular arrangement is suggested by the number of surrounding molecules? The physical molecular arrangement is suggested by the number of surrounding molecules is tetrahedral arrangement (c) the motions of molecules Motions of molecules is random thermal motion (d) the state of order/disorder of molecules Highly exothermic reactions tend o take place spontaneously. However, weak exothermic reactions and some endothermic reactions can also occur spontaneously. Sometimes these reactions will proceed under stronger reaction conditions, such as a temperature increase. The products have a higher enthalpy than the reactants. Therefore, since energy is absorbed in this process, is positive. It has been determined experimentally that if 1 mole of carbon reacts with 1 mole of steam, then =131kJ. Most spontaneous reactions seem to have negative value. Since is positive in this reaction, some additional factor must be involved. This additional factor is the degree of disorder or entropy. We have seen in chapter 16 that there is a very orderly arrangement of atoms in crystalline solids. In liquids, there is less order. Two liquids dissolved in each other make a more disordered system than the two liquids separated. Gases lack any orderly arrangement. a gas at high temperature is more disordered than one at a low temperature. The degree of disorder, or entropy, is represented by the symbol S. entropy is a state function. In the reaction , there are more particles after the change than before. Consequently, the products represent a more disordered system. Another way of considering entropy is the probability of finding a particular object in a specific place. In the liquid state, water molecules have no systematic arrangements. However, the water molecules are close together, so we might expect to find a water molecule almost anywhere we looked in a container of liquid water. On the other hand, we know that the molecules of vapour are quiet far apart.. Thus, the entropy of the gas is greater than that of of the liquid. (e) pressure and energy and the relationship between the two. The relationship is non-linear relationship between pressure and energy b) Click on the RDF (Radial Distribution Function) button at the bottom of the simulator. Wait for about 5 minutes for the plot to stabilise, take a snapshot, paste it in your answer, and label it ‘RDF at T = 10’. Answer the following two questions: i. Why do you need to wait about 5 minutes for the plot to ‘stabilise’? One waits for 5 minutes for plot to stabilise due to the fact that simulation is on going and it may take around 5 minutes to be complete. ii. What do the peaks and troughs tell you about the structure of this system at this low temperature? The structure is not stable c) Close the RDF window and click on the MSD (Mean Square Displacement) button and wait for about 5 minutes before taking a snapshot and pasting the resulting plot in to your answer. Label the plot ‘MDS at T = 10’. While you wait, describe how the last atom that you picked moves, how far it goes and the effect that the other atoms have on its motion. d) Increase the temperature to its maximum value (1000) From the graph it can be noted that when the temperature is high the troughs and peaks are more pronounced. As we raise the temperature of a bar of iron from room temperature to 100 the atoms gain energy and move more rapidly. As a result, although their organization in a crystal lattice remains, the increased motion means that an atom is less likely to be found in a particular spot as often as before. Entropy is increased when the bar is heated. Change in entropy is symbolized as. A positive value for system for a means and increase in the degree of disorder. That is to say, the system becomes less ordered. Such a change occurs when a solid is converted to a liquid or a gas. When liquid or gas is converted to solids, is negative. e) Select one atom and try to figure out how many atoms are in its immediate vicinity. What has changed upon increasing the temperature? There are 4 atoms are in its immediate vicinity. When the temperature was increased number of atoms reduced f) Click on the MSD button and wait for about 2 minutes before you paste the resulting plot on to your answer. Label the plot ‘MSD at T=1000’. While you wait describe how the last atom that you picked moves, how far it goes and the effect that other atoms have on its motion. g) Change the temperature to 500 (with the same density at 0.7) and generate both RDF and MSD plots, wait at least 2 minutes before pasting the plots on to your answer question and label the plots ‘RDF at T=500’ and ‘MSD at T=500’ respectively h) Change the temperature to 200 (density at 0.7) and generate both RDF and MSD plots, wait at least 2 minutes before pasting the plots on to your answer. Label the plots ‘RDF at T=200’ and ‘MSD at T=200’ respectively. i) Compare all three MSD plots (at temperatures of 1000, 500 and 200) and explain how the change in temperature (at constant density) has affected the diffusion of the atoms. Estimate the slopes (from the linear portion of the plots) and take those values to represent the diffusion rate. Now plot the diffusion rate (D) against the inverse of the temperature (D vs 1/T). A straight line on this plot would indicate that the diffusion process is the same over the temperature range considered. Paste your Diffusion vs 1/T plot into your answer. j) Compare all three RDF plots (at temperatures of 1000, 500 and 200) and explain how the change in temperature has affected the structure of the system. What has happened to the shape of the peaks and troughs? What do you think this means? When the temperature is high the curve shifts to right when it is low it shift to the left k) For the last experiment you will attempt to ‘make rain’. Take the temperature to an intermediate value (~500) and the density to its minimum (0.06). This could be seen as creating water vapour. Wait for a while (~30 seconds) before slowly (over about a minute) reducing the temperature to about 50 (make sure that it’s not at its absolute minimum). You will now have to visually inspect the system over 10 to 15 minutes. Describe what occurs to the system during this time and at the end of this time. If you see groups of atoms, what do you think they represent as far as water is concerned? Are these groups of atoms ordered or disordered structures? The compounds in a series have the same general formula. The formula of one member in the series differs from the formula of the next member by. All compounds in the series have similar chemical properties. There is a gradual change in the physical properties of the compounds in the series as the number of carbon atoms in the molecules increases. Polar water molecules are attracted to ions in a crystal structure and can surround them. The attraction can be so great that the forces holding ions together are overcome. The ions become together are overcome. The ions become free to move in solution surrounded by water molecules. The negative ends of the water molecules are attracted to the positive ions, and the positive ends to the negative ions. Water molecules attract each other, and weak bonds form between molecules.Oxygen atoms are attracted to hydrogen atoms. Although the bonds are weak compared with the bonds within the molecules, they are stronger than is normal between molecules. The weak bonds are called hydrogen bonds.. The attraction of water molecules for each other accounts for the relatively high melting and boiling points of water. 8. The use of potential energy function and its parameters The use of potential energy function which is written as PER (R) = Non-bonded atom pairs i,j Where R is the co-ordinate vector, K is the stretching constant, b is the bond rent, and PEF(R) is potential energy function. From the above statement the parameters have been determined as bond stretching constants, equilibrium bond rent, bond structure, co-ordinate vector, number of bonds, angle bending, out-off plane distortions, dihedral terms. In terms of molecular mechanics, potential energy is used in boding the molecules and the function is used to determine the amount of energy that is required to free the bonding structure. It also helps to understand how molecules of proteins can be released. Read More

Each element has its own characteristic emission spectrum. For instance, the characteristic red colour of neon sign is caused by the emission spectrum of neon. Scientists soon began to use spectroscopy to identify the elements present in substances. Many previously unknown elements were discovered through spectroscopy. Cesium was named fro its bright blue spectral lines; rubidium was named for its prominent red lines. Turning their spectroscopes toward the sun and stars, scientists identified elements such as helium, which had not yet been discovered on earth.

The spectra of most elements show no obvious pattern but hydrogen-the simplest atom-does show a striking pattern. 3. Figure below shows how the dipole within a water molecule may be Represented. A. Use Figure to show the parallel orientation of the dipoles of two water molecules B. Use Figure 1 to show the antiparallel orientation of the dipoles of two water molecules (0.5 marks) C. The formula for a dipole-dipole interaction energy is as follows: E = µ1µ2θ’/Dr3 – {3(µ1r θ’’)(µ2r θ’’)}/Dr3 Where E = potential energy of the dipole-dipole interaction µ1µ2 are dipole moments of dipole 1 and 2 respectively θ’ and θ’’ are functions of the orientation (angles) of the dipoles relative to each other D is the dielectric constant of the medium r is the distance between molecules This formula can be seen as a ‘left hand’ part and a ‘right hand’ part.

The right hand part is a subtraction of {3(µ1rθ’’)(µ2rθ’’)}/Dr3. Describe the general relationship of potential energy to the parameters and variables shown by the ‘left hand’ part of the dipole-dipole interaction formula. The relationship of potential energy to the parameters and variables shown by the ‘left hand’ is of non-linear nature. D. Use the Excel spread sheet to calculate the relationship between interaction energy and distance in a dipole-dipole interaction between the two water molecules when: (i) their dipoles are oriented antiparallel to each other. (ii) their dipoles are oriented parallel to each other. (1 mark) (iii) Briefly explain how we can seemingly ‘ignore’ the ‘right hand’ part of the dipole-dipole interaction formula to describe the general relationship of a dipole-dipole interaction. E. Can a dipole-dipole interaction be considered a short, medium, or long range interaction? Explain. Dipole-dipole interactions can be short-range interactions because energies between the falls off as 1/r3 power.

Meaning that they have a complicated angular-dependence, 4. Discuss the following statement: “The relationship between structure and function appears to be a many-many relationship”. What does this statement mean and what issues does this involve for discovering the function of a protein? You may use tables to describe this structure to function issue. Many-many relationships of protein molecules imply that the chemical structure is connected to many molecules therefore breaking the bond become difficult.

Some of the structures are bonded. Many-many relationship means that discovering the functions of a protein will require more energy than when it is many-one or one-one. 5. The structure superposition of two or more protein structure and determination of evolutionally relatedness. Protein structure re-alignment is important in determining the relationship between two proteins from the way it is arranged. If the structural alignment similarity will indicate some evolutionary relationship between the two proteins.

This is also important when determining the source of the protein. One needs to do sequence structure mapping in order to determine whether they are related. It’s no secret that this system of re-alignment is used to determine the evolutionary relationship. The following formula is used to determine structural re-alignment: 6) i). structural bioinformatics involves the use of protein RNA and DNA structures to understand the biological processes.

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