Assignment 1: visualization and ranking of protein conformations  (Page 3/5)

Clean up your VMD window by deleting or hiding the loaded molecule. To delete it, right click the molecule name in the "VMD Main" window and select "Delete Molecule."Now load the all-atom .pdb we provided. Right click the molecule name in the VMD window and select "Delete Frames." Click "Delete" in the window that pops up. Load the prepared .crd file 1coa_confs.crd, which is included in the .zip archive linked at the top of this webpage, by selecting "File->Load Data into Molecule." The native conformation for 1COA is the first conformation specified in"1coa_confs.crd" As the .crd file is loading, you will see VMD render each conformation in series.You can visualize this series of conformations as an animation, which is the default behavior of VMD, but in this case, it makes more sense to view the conformations superimposed over each other. You can superimpose conformations from the .crd file by using the "Graphical Representations" menu's "Trajectory" tab, where you can tell VMDto draw multiple frames in the format a:b, where a is the number of the first frame you want to superimpose, and b is the number of the last frame (numbering starts at 0). You should be able to see something similar to Figure 2. Warning: If the machine you are working on is relatively old or slow, do not attempt to display more than 50-100 structures simultaneously. More than that could cause VMD to become unresponsive.

B. molecules in motion

Molecular Dynamics simulations model the motion of a molecular system using a force field based on the chemical properties of the atoms involved, and updates its state at each moment in time using Newton's Laws of Motion (classical mechanics). You will now visualize the conformations visited by HIV-1 protease during a short MD simulation. The corresponding native structure is available inhiv_native.pdb, in the .zip archive for this assignment. Load the native structure .pdb and then the trajectory (.crd) file hiv_md_simulation.crd in assignment1.zip (unzip it first), in the same way that you loaded 1coa_confs.crd in the previous section, to visualize the conformations produced by the MD simulation. Once the full series of structures is loaded, you can view them as an animation by selecting the "Loop" or "Rock" option in the leftmost pulldown menu at the bottom of the "VMD Main" window and then clicking the forward or reverse buttons (bottom right or bottom left corner of the "VMD Main" window). You should use the "bonds", "lines" or "licorice" representation for this file. This animation should give you afeeling for the flexibility of HIV protease.

Note that you can always save your work session in a state .vmd file. This can be very convenient if you do not want to repeat all the graphicalrepresentations you have already chosen for 1COA. Please visit the manual for details on how to save and resume a session.

Ranking conformations

The conformations you superimposed on one another look different from the native conformation. We will look at one possible way to quantify the difference orsimilarity between two conformations: LRMSD (Least Root Mean Squared Deviation). This is a measure of the average of the distance each atom would have to move to convert one structure to the other. In this assignment you will use a standard script that computes the LRMSD betweenthe conformations already loaded in a trajectory in VMD from a reference conformation. Please download the Tcl script to compute the RMSD of conformations from a reference conformation. You may want to modify the script to print to a file of your choice. You can do this by modifying the line that opens the file ( set fp [open "rmsd_output.txt" w] ). If you prefer to print to the screen, you can increase the buffer size of the Tk console in VMD typing tkcon buffer xxxx inside the console itself, where xxx is the number of lines to store. As an alternative, you may use the Matlab script rmsd.m included with the files for the assignment. Note that this script requires the other three .m files to be in the same directory, and that it assumes that the first line of all .crd files is a comment that can be discarded. Please answer Q4 .