Exercise 10
Key ... 110 pts
 
 

{A. Insight II on an SGI Computer}

{1. Logon to an SGI computer and activate Netscape Communicator}

{2. Activate Insight II}

{3. Insight II documentation}
Comments on Insight II documentation ??? [5 pts]
 
 

{B. The Insight II tutorial "Getting Started with Insight II"}

{1. Activate the Insight II tutorial "Getting Started with Insight II"}

{2. Do the Insight II tutorial}

{a. The "cheaters" way of doing the Tutorial}

{b. A "better" way of doing the Tutorial}

{c. The first Three Pages of Commands in the Tutorial: use of Lysozyme}

{d. Include comments in your Notebook}
Some comments on specific issues with the tutorial ... [10 pts]

{e. Answer the Questions as you proceed through the Tutorial}
 
 

{C. Questions: }

1. What is Insight II and what does it do? [6 pts]
InsightII is a 3D graphical environment for molecular modeling, best know for protein work, that runs on Silicon Graphics (SGI) workstations. It creates, modifies, naipulates, displays, and analyses molecular systems and related data.

2. What are the modules in the Insight II package, and what do each do? [6 pts]
Insight II has many modules; see URL http://www.accelrys.com/insight/
Also see the URL: http://www.accelrys.com/pdf/insight/i2_integrated_modeling_env.pdf
2 pts each for any three, including something about their function or purpose:
Builder, Biopolymer, DelPhi, Solvation, Discover, Discover_3, CHARMm, Docking, Ludi, Homology, Binding_site, Ampac/Mopac, DMol, Turbomol, Zindo, QuanteMM

3. What are 4 additional applications in the MSI package, and what does each do? [8 pts]
Many possibilities here also, see URL:   http://www.accelrys.com/
Some of these include:  Quant and CNX for protein x-ray crystallography, FELIX for NMR, Cerius@ for protein simulation; GCG and MacVector for sequence analysis; SeqLab and SeqWeb for graphical interfaces
 

4. How does one use the mouse to translate and rotate a protein model? [3 pts]
To translate, use the middle button: the model moves in the direction of mouse movement.
To rotate, press the right button; rotation occurs in the direction of mouse movement

5. How are rotations in each of the three dimensions (about x,y,z axes) correlated with motion of the mouse? [6 pts]
In ways that are strange to determine .... two motions of the mouse for rotations about three axes ...

6. In what three different ways does one make choices using the pulldown menus? [6 pts]
a) click on the choices in the pulldown menu
b) click on a check box
c) type in a name in a given box ...

7. What is the comparable way of making choices using the command line? [3 pts]
Type in the names of the commands on the command line.  Spaces occur between some and not others.  If a command is NOT chosen, use a minus sign in front of it.

8. What is the function of the Temperature Spectrum? [3 pts]
This shows the relative reactivity of each type of amino acid residue.

9. What happends to the cylinders and ribbons when you rotate the molecule?  why is this? [6 pts]
They become stick characters from the solid, blended characters, and are all of one color.  This is to save computation time during the redraw operations in the rotations.

10. How are hydrogen atoms represented in Insight II? [3 pts]
They are represented by horizontal-vertical crosses ...

11. What is a subset of atoms and how are such used in Insight II? [4 pts]
A subset of atoms is a group of atoms involved in common structure or function.  Insight II uses such from graphical depiction of structure or function.

12. How is the subset called ACTIVE_SITE used in the tutorial? [3 pts]
This is used as an example of a subset, whose surface is solified, to show the surface of the lysozyme active site.

13.  What are the three numbers used to choose a "color" in Insight II such as used in the color for the active_site atom subset? [3 pts]
These show the relative mixtures of the three primary colors (red, yellow, blue) used to give the chosen color.

14. What "Molecular_Spec" was used in the "Create Surface" operation for the Active Site, and why? [3 pts]
The Molecular_Spec is the "active_site" subset of the Lysozyme residues, the subset of which one wishes to create the surface graphic.

15. Why does the solid surface become a series of dots when the molecule is rotated? [3 pts]
Same as Q.7 ... to save computation time during the redraw opearations in the rotations.

16. What are the four steps in displaying the electrostatic potential in color of the active site surface?  Include the purpose of each step in your answer. [8 pts]
The first 3 steps create, compute, and display the grid using the Docking module.  This grid, called ACTIVE_SITE_VGRD, is the framework for the electrostatic potential.  The first step creates this grid; the second computes within the grid the electrostatic potential values, the third displays these.  The fourth step converts the displayed values into color values which then are displayed on the active_site surface.

17. Why are the colors of the surface then adjusted? [3 pts]
The contrast is initially low; the colors are adjusted to fit a max and min that more closely fits the electrostatic potential values, thereby permitting use of a wider color spectrum.

18. Comment on the logic of the steps in building small docking molecules. [3 pts]
This is done excruciatingly slowly, step by step, identifying each atom involved in forming each covalent bond, with subsequent changes in angles and translation and rotation relative to the protein, as needed for docking.

19. What is the substrate of Lysozyme, and how does the molecule you constructed mimic this substrate? [6 pts]
Substrate is the peptidoglycan layer of bacteria, a crosslinked molecule of amino acids and carbohydrate; lysozyme cleaves linkages between glucose moities. The constructed molecule contains a couple of monosaccharide residues joined in the linkage cleaved hydrolytically by lysozyme.

20. Based on this substrate, why do you think tears from eyes are a good source of lysozyme? [3 pts]
Lysozyme is found at high concentration in tears to lyse bacteria that land on the surface of your eyes.

21. What does the energy minimization step in the Discover module do? [6 pts]
This uses an iterative descent algorithm to minimize the energy of the structure.  In so doing, it modifies angles slightly to yield a structure with energy equal to that of the closest local minimum.  Here we use 100 iterations in this step.