CHM 579 Assignment #5
Molecular Simulations - Molecular Dynamics of heterogenious systems
Due on Monday, March 27, 2020 at 11:59 PM
Part 1 - Molecular Dynamics with NAMD & VMD
This part of the assignment deals with running simulations and understanding how to analyze output from Molecular Dynamics (MD) simulations. The output of a MD program is a series of time-resolved coordinates for all of the atoms in the simulation. The code widely used in the MD community is GROMACS. It is one of the fastest MD software out there. Due to the complexity of using the code (only for Linux and MacOS and assumes Linux/Unix background), it would not be fair for all students to run simulations with it. Thus, we have decided to use NAMD, a MD simulation program developed by Theoretical and Computational Biophysics Group at UIUC in conjunction with VMD, the molecular viewing program. VMD has the capability to work with NAMD in order to display the results of a simulation as they are calculated (Interactive MD). As new atomic coordinate timesteps are generated by the simulation process, they can be transferred directly over to VMD, which can then animate the molecule. A major new feature in VMD is the ability to add perturbative steering forces to a running simulation, which are incorporated directly into the dynamics calculation. You will run both Interactive MD and Steered MD for this assignment.
In order to complete this assignment, you will require to have up-to-date
versions of the following software, properly installed on your computer, as mentioned on the NAMD tutorial website:
For windows users, a proper work path should be set for the installed softwares.
Suppose these softwares are installed under the following directories:
- VMD: a molecular graphics program.
This software is developed by the Theoretical and Computational Biophysics Group.
You can download it for free from VMD website. We encourage you to
go through the VMD tutorial at VMD website and also the VMD tutorial, which we created prior to using the NAMD tutorial mentioned below. You should have experience with VMD from Assignment #1. You will need some extensions for using NAMD with VMD for Interactive Molecular Dynamics (IMD) which can be found in the tutorial at VMD website.
- NAMD: a molecular dynamics simulation program. This software is also
developed by the Theoretical and Computational Biophysics Group. You can download
it for free from NAMD website.
- A text editor: We have a few easy-to-use recommendations.
- UNIX: vi editor, emacs, any other editor you prefer
- Mac OS X: Terminal, TextEdit (included with OS)
- Windows XP: WordPad (included with OS).
- A command prompt:
- UNIX: Terminal
- Mac OS X: Terminal.app
- Windows XP: DOS command prompt.
- VMD: C:\Program Files\University of Illinois\VMD,
- NAMD: C:\NAMD,
The work path can be created in different ways. One can either append
the following command in C:\autoexec.bat and execute it or
type this command in a DOS prompt:
path=C:\Program Files\University of Illinois\VMD;C:\NAMD;
Part 1A: Deca-alanine in vacuum
To make things simple for you we have chosen a tutorial from the NAMD website which you can replicate with different parameters and actually run simulations on your computer. You would be simulating deca-alanine in vacuum. A biologically relevant simulation would involve water molecules but in this case one can get to know a lot about structural features in deca-alanine in vacuum as time progresses in the simulation.
The deca-alanine tutorial will get you started with NAMD. You can get the pdf file for the tutorial here. Please NOTE that only pages 1-11 are relevant in the tutorial, though you can read further to get an idea of TCL. A feature of NAMD is that we can use TCL scripting language for analysis and simulation. We do not expect you to do any programming in TCL for the purpose of this assignment. Thus, we would be providing all the files needed to start the simulation. You should use VMD Extension for analysis as mentioned in the VMD tutorial on the VMD website. Please feel free to look for any good tutorials for VMD analysis for MD online, but ALWAYS reference it. We would try to update the VMD tutorial as well, to help with this assignment. You would only need to change the parameters for different simulations as asked below:
- Download and install the latest version of VMD and NAMD on your computer. Download the tar-zipped set-up files to get you started with the simulation. Please make sure that the current directory contains all the files downloaded. For windows users, create a folder files and download all the set-up files in this directory. At the command prompt make files as the current directory.
- The Interactive MD is for you to see how does the deca-alanine behaves with simulation. Follow the instructions in the tutorial for Interactive MD:
- See how the molecule behaves as the simulation progresses. Play with putting the forces on different atoms etc. and see what happens.
- The file imd.namd is the simulation parameter file used by NAMD for Interactive MD. To view the simulation longer, change the parameter run (the last line of the file) from 100000 to 1000000 (these are the number of steps in simulation). As the timestep parameter in the imd.namd file is set to 2 fs, the simulation with 100000 steps is 200ps and with 1000000 steps is 2 ns. The parameter temperature is the temperature at which the simulation takes place, which is set to 300K, i.e. room temeperature. Note that as you increase the number of steps for simulation, the longer it will take for the simulation to stop. Thankfully there is a Stop Simulation button in VMD for the interactive mode. Feel free to change any parameters you want and see the effect of changing parameter with MD. This interactive simulation helps you understand how the alpha-helix behaves and would help you answer the following questions:
- Is the deca-alanine stable in vacuum at room temperature?
- What is the effect of temperature on simulation, i.e. what do we expect when we increase the temperature from 300K to 400K and 450K?
- Can we change the temperature and achieve refolding of the deca-alanine?
- During unfolding of the alpha-helix, does it unfold from one end or from both ends or the center of the deca-alanine. Why?
- Run Steered Molecular Dynamics (SMD) for 500 ps on deca-alanine in vacuum at 300K, 400K and 450K by changing the parameters in the smd.namd file. Note this is not an interactive MD but you should analyze the MD trajectory using VMD. You will notice that the SMD uses smd.tcl file for the force it applies on the atoms in simulation as explained on page 9 of the tutorial. Feel free to change the force-constant (k) paramter in the smd.tcl file to make the simulation work for 500ps.
- Plot the following using VMD for each temperature of simulation and explain your observation for each plot in 2-3 sentences:
- Obtain Ramachandran plots for the first and last frame using VMD. See if you can find something interesting at some point between the start and then end of the trajectory.
- Graph end to end distance during the simulation vs Time for all temperatures.
- Graph Force vs Time for all temperatures.
- Graph % Helicity vs Time for all temperatures. (We are not looking for a quantitative estimate, a qualitative plot of secondary structure is fine for this)
- Graph RMSD vs Time for all temperatures.
- Graph Potential Energy vs Time for all temperatures.
- Graph Number of Hydrogen Bonds vs Time for all temperatures. (use the definition of hydrogen bonds as mentioned in the deca-alanine tutorial).
For number of Hydrogen bonds with time, we made a simple TCL script which can be used to get the numHbonds. Please save this file in your current directory with all the output and input for NAMD. When you load your trajectory in VMD, go to Analysis and then TK Console. Make sure that the path to this is the path of your NAMD working directory ( i.e. where you have your simulation input and output files). You can get the output for the number of H-bonds with time, in the file numHbonds.dat when you invoke the command in the Tk console:
Please refer to the tutorial if you have problems with using tk console. You can then use the plot command in the console or open this file in Excel (or your favorite plotting program) and plot the number of hydrogen bonds with time.
- Answer the following questions:
- From the above plots, approximately how much force is needed to unfold the alpha-helix at different temperatures? Are these forces different, why?
- Describe in a few sentences what do you expect when water is added to the system -- How does temperature play a role when water is added? What happens to the alpha-helix? Is it still stable in water?
- Please note that running the simulation once does not give accurate results in comparison to the experiments. Thus, always in MD, an ensemble average is taken for any property of the system analyzed. As the purpose of this assignment was to get you fimiliar with MD, doing multiple simulations for different starting configurations of the system is beyond the scope of this assignment.
Part 2 - Molecular Dynamics set-up with Gromacs
This part of the assignment deals with running simulations and understanding how to set-up simple systems with Gromacs and understand the output from Molecular Dynamics (MD) simulations. For this part of the assignment, please follow the instructions in the PDF files given below and answer the questions asked in the files:
Note that the file required to do this assignmnet is here.
Please feel free to email the instructor if you have any questions about this assignment. Start early!!!
Handing Things In:
- Please remember to properly cite scientific papers/web pages
you used for your assignment! You can find the reference to VMD, NAMD and GROMACS on their website. It is required to cite these references if you are using VMD or NAMD in your assignment. Plagiarism will not be tolerated. It is OK to include some well-written quotes in your assignment, but your descriptions should be mostly in your own words, so we can evaluate your understanding of
How You Will Be Graded
- You answer all the questions asked on this page as well as in the linked PDF files of tutorials and labs.
- It is important to show that you understand things and not merely say 'yes' or 'no' for answers to the questions and grading will be done on your reasons/explanations to things that are asked in this assignment.
- Feel free to include any movies and illustrations for all parts of the assignment. Like we have discussed - think of the assignment as a research online paper where you can include illustrations to elaborate the points you are making as part of your results and discussions.
Problems? Questions about the Page or the Class? Contact